Compounds having 4-pyridylalkylthio group as a substituent

ABSTRACT

A compound having the following formula [I] or a pharmaceutically acceptable salt thereof: 
                         
wherein A is an aromatic five-membered heterocycle which optionally is fused with a cycloalkane ring; B is an alkylene; R 1  and R 2  are hydrogen, hydroxyl, alkoxy, aryloxy, alkyl, cycloalkyl, aryl, heterocycle, amino, alkylamino, arylamino or acyl, or R 1  and R 2  join together to form a heterocycle; X and Y are hydrogen, halogen, hydroxyl, alkoxy, aryloxy, alkyl, cycloalkyl, aryl, mercapto, alkylthio, arylthio, carboxyl, an ester of carboxyl, an amide of carboxyl, cyano or nitro; p is 0, 1 or 2; and q is 0 or 1. The compound is useful for treating diseases in which angiogenesis or augmentation of vascular permeability is involved.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of application Ser. No.12/381,290 filed Mar. 10, 2009 (U.S. Pat. No. 8,207,194), which is adivisional application of application Ser. No. 10/548,283 filed Sep. 1,2005 (U.S. Pat. No 7,534,802), which is a U.S. national phaseapplication under 35 USC 371 of International applicationPCT/JP2004/002812 filed Mar. 5, 2004. The entire contents of each ofapplication Ser. Nos. 12/381,290, 10/548,283 and Internationalapplication PCT/JP2004/002812 are hereby incorporated by referenceherein.

TECHNICAL FIELD

The present invention relates to novel compounds having a4-pyridylalkylthio group as a substituent or salts thereof which areuseful as pharmaceuticals. These compounds are useful as therapeuticagents for diseases in which angiogenesis or augmentation of vascularpermeability is involved, particularly as therapeutic agents for cancer,rheumatoid arthritis, age-related macular degeneration, diabeticretinopathy, retinopathy of prematurity, retinal vein occlusion,polypoid choroidal angiopathy, diabetic macular edema, psoriasisvulgaris, pultaceous arteriosclerosis and the

BACKGROUND ART

Angiogenesis is a phenomenon wherein a new vascular network is formedfrom existing blood vessels and is observed mainly in fine blood vessel.Angiogenesis is originally a physiological phenomenon and is essentialfor blood vessel formation at a viviparous period, but it is usuallyobserved only at a limited site such as endometrium or follicle or at alimited period such as a wound healing process in adults. However,pathologic angiogenesis is caused in diseases such as cancer, rheumatoidarthritis, age-related macular degeneration, diabetic retinopathy,retinopathy of prematurity, retinal vein occlusion, polypoid choroidalangiopathy, diabetic macular degeneration, psoriasis vulgaris andpultaceous arteriosclerosis, and pathologic angiogenesis closely relatesto the progress of pathema of these diseases. It is considered thatangiogenesis is adjusted by balance between its promotive factor andinhibitory factor, and angiogenesis is caused by losing of the balance.(See Molecular Medicine vol. 35, special issue, “Molecular Mechanism ofSymptom and Pathema”, Nakayama Shoten, 73-74 (1998) and Protein, NucleicAcid, Enzyme, extra number, “The Most Advanced Development of NewDrugs”, Kyoritsu Shuppan; 1182-1187 (2000).)

A vascular endothelial growth factor (hereinafter abbreviated as “VEGF”)is a factor which specifically acts on a receptor (Flt-1, KDR/Flk-1 orthe like) existing on the surface of vascular endothelial cells, therebypromoting growth and migration of the vascular endothelial cells,construction of a capillary vessel network due to vasculogenesis. VEGFalso augments vascular permeability, and plays an important role inoccurrence of angiogenesis. Accordingly, there have been many reports onattempts to treat diseases in which angiogenesis and the augmentation ofvascular permeability are involved by inhibiting VEGF to control theoccurrence of angiogenesis and the augmentation of vascularpermeability. Examples of drugs to be used for the treatment are2-indolinone derivatives (WO 98/50356), phthalazine derivatives (WO98/35958), quinazoline derivatives (WO 97/30035), anthranilic acid amidederivatives (WO 00/27819), 2-aminonicotinic acid derivatives (WO01/55114) and the like. However, compounds which have 4-pyridylalkylthiogroup as a substituent aren't described in these patent documents atall.

On the other hand, Il Farmaco-Ed. Sc., 18, 288 (1963) and WO 02/066470report compounds having chemical structures relatively close to those ofthe compounds having 4-pyridylalkylthio as a substituent. The compoundsdisclosed in Il Farmaco-Ed. Sc., 18, 288 (1963) are benzoic acid amidederivatives having 3-pyridylalkylthio, and antibacterial actions arerecited as their use. WO 02/066470 relates to substituted alkylaminederivatives and their pharmaceutical use, and discloses compounds havingenormous combinations of chemical structures. WO 02/066470 discloses aderivative having 4-pyridylalkylamino as one example among thosecompounds, but does not describe 4-pyridylalkylthio derivatives at all.

DISCLOSURE OF THE INVENTION

It was a very interesting subject to study synthesis of novel compoundshaving 4-pyridylalkylthio as a substituent and to find pharmacologicalactions of the compounds.

Studying synthesis of the novel compounds having 4-pyridylalkylthio as asubstituent, the present inventors succeeded in preparing many novelcompounds. Further, studying variously pharmacological actions of thesecompounds, they found that the compounds have cell growth inhibitoryeffects, tumor growth inhibitory effects, paw edema inhibitory effectsor choroidal neovascularization inhibitory effects, and are useful astherapeutic agents for diseases in which angiogenesis or augmentation ofvascular permeability is involved, particularly as therapeutic agentsfor cancer, rheumatoid arthritis, age-related macular degeneration,diabetic retinopathy, retinopathy of prematurity, retinal veinocclusion, polypoid choroidal angiopathy, diabetic macular edema,psoriasis vulgaris, pultaceous arteriosclerosis and the like to completethe present invention.

The present invention provides the novel compounds having4-pyridylalkylthio as a substituent or salts thereof which are useful aspharmaceuticals. In particular, the novel compounds having4-pyridylalkylthio as a substituent of the present invention haveexcellent cell growth inhibitory effects, tumor growth inhibitoryeffects, paw edema inhibitory effects or choroidal neovascularizationinhibitory effects, and are useful as therapeutic agents for thediseases in which angiogenesis or augmentation of vascular permeabilityis involved, for example, cancer, rheumatoid arthritis, age-relatedmacular degeneration, diabetic retinopathy, retinopathy of prematurity,retinal vein occlusion, polypoid choroidal angiopathy, diabetic macularedema, psoriasis vulgaris, pultaceous arteriosclerosis and the like.

BEST MODE FOR CARRYING OUT THE INVENTION

The present invention relates to compounds represented by the generalformula [I] or salts thereof (hereinafter referred to as “the presentcompound” as far as there is no proviso) and pharmaceutical compositionscomprising the present compound. In more detail, the present inventionrelates to therapeutic agents comprising the present compounds as activeingredients for diseases in which angiogenesis or augmentation ofvascular permeability is involved, for example, as therapeutic agentsfor cancer, rheumatoid arthritis, age-related macular degeneration,diabetic retinopathy, retinopathy of prematurity, retinal veinocclusion, polypoid choroidal angiopathy, diabetic macular edema,psoriasis vulgaris, pultaceous arteriosclerosis and the like,

wherein the ring “A” is a benzene ring, or an aromatic five-memberedheterocycle or an aromatic six-membered heterocycle which can be fusedwith a cycloalkane ring;“B” is alkylene;R¹ and R², the same or different, are hydrogen, hydroxy, substituted orunsubstituted alkoxy, substituted or unsubstituted aryloxy, substitutedor unsubstituted alkyl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted aryl, substituted or unsubstitutedheterocycles, amino, substituted or unsubstituted alkylamino,substituted or unsubstituted arylamino, or substituted or unsubstitutedacyl;R¹ and R² can join together to form a substituted or unsubstitutedheterocycle;X and Y, the same or different, are one or plural groups selected fromhydrogen, halogen, hydroxy, substituted or unsubstituted alkoxy,substituted or unsubstituted aryloxy, substituted or unsubstitutedalkyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted aryl, mercapto, substituted or unsubstituted alkylthio,substituted or unsubstituted arylthio, carboxyl or ester thereof oramide thereof, cyano and nitro;

-   p is 0, 1 or 2; and-   q is 0 or 1.    The same definitions are applied hereinafter.

The respective groups defined above are described in detail below.

The cycloalkane ring is a cycloalkane ring having three to eight carbonatoms. Specific examples of cycloalkane rings are a cyclopropane ring, acyclobutane ring, a cyclopentane ring, a cyclohexane ring, acycloheptane ring, a cyclooctane ring and the like.

The aromatic five-membered heterocycle is a monocyclic aromaticfive-membered heterocycle having one to three heteroatoms selected froma nitrogen atom, an oxygen atom and a sulfur atom in the ring. Specificexamples of aromatic five-membered heterocycles are a pyrrole ring, apyrazole ring, an imidazole ring and a [1,2,3]triazole ring, which havenitrogen atom(s) in the ring; a furan ring, which has an oxygen atom inthe ring; a thiophene ring, which has a sulfur atom in the ring; anoxazole ring and an isoxazole ring, which have a nitrogen atom and anoxygen atom in the ring; and a thiazole ring and an isothiazole ring,which have a nitrogen atom and a sulfur atom in the ring, preferably apyrazole ring, a furan ring and a thiophene ring, more preferably athiophene ring.

The aromatic five-membered heterocycle fused with the cycloalkane ringis a fused ring wherein the aromatic five-membered heterocycle is fusedwith the cycloalkane ring.

The aromatic six-membered heterocycle is a monocyclic aromaticsix-membered heterocycle having one to four nitrogen atoms in the ring.Specific examples of aromatic six-membered heterocycles are a pyridinering, a pyridazine ring, a pyrimidine ring, a pyrazine ring, a[1,2,3]triazine ring, a [1,2,4]triazine ring and [1,2,3,4]tetrazinering, preferably a pyridine ring and a pyrazine ring, more preferably apyridine ring.

The aromatic six-membered heterocycle fused with the cycloalkane ring isa fused ring wherein the aromatic six-membered heterocycle is fused withthe cycloalkane ring.

The alkylene is straight-chain or branched alkylene having one to eightcarbon atoms. Specific examples of alkylene are methylene, ethylene,propylene, tetramethylene, pentamethylene, hexamethylene,heptamethylene, octamethylene, methylmethylene, dimethylmethylene,2-methyltrimethylene and the like.

The alkoxy is straight-chain or branched alkoxy having one to eightcarbon atoms. Specific examples of alkoxy are methoxy, ethoxy,n-propoxy, n-butoxy, n-pentoxy, n-hexyloxy, n-heptyloxy, n-octyloxy,isopropoxy, isobutoxy, sec-butoxy, tert-butoxy, isopentoxy and the like.

The alkyl is straight-chain or branched alkyl having one to eight carbonatoms. Specific examples of alkyl are methyl, ethyl, n-propyl, n-butyl,n-pentyl, n-hexyl, n-heptyl, n-octyl, isopropyl, isobutyl, sec-butyl,tert-butyl, isopentyl and the like.

The cycloalkyl is cycloalkyl having three to eight carbon atoms.Specific examples of cycloalkyl are cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and the like.

The aryl is a monocyclic or fused polycyclic aromatic hydrocarbon or afused polycyclic hydrocarbon formed by condensation with a cycloalkanering. Specific examples of aryl are phenyl and the like, which are themonocyclic aromatic hydrocarbons; naphthyl, anthryl, phenanthryl and thelike, which are the fused polycyclic aromatic hydrocarbons; and indanyl,tetrahydronaphthyl, tetrahydroanthryl and the like, which are the fusedpolycyclic hydrocarbons.

The aryloxy is monocyclic or fused polycyclic aromatic hydrocarbon oxyhaving 6 to 14 carbon atoms or fused polycyclic hydrocarbon oxy formedby condensation with a cycloalkane ring. Specific examples of aryloxyare phenoxy and the like, which are the monocyclic aromatic hydrocarbonoxy; naphthoxy, anthroxy, phenanthroxy and the like, which are the fusedpolycyclic aromatic hydrocarbon oxy; and indanoxy, tetrahydronaphthoxy,tetrahydroanthroxy and the like, which are the fused polycyclichydrocarbon oxy.

The heterocycle is a saturated or unsaturated monocyclic heterocycle orfused polycyclic heterocycle having one to four heteroatoms selectedfrom a nitrogen atom, an oxygen atom and a sulfur atom in the ring.

Specific examples of saturated monocyclic heterocycles are pyrrolidine,piperidine, homopiperidine, piperazine and the like, which have nitrogenatom(s) in the ring; tetrahydrofuran, tetrahydropyrane, dioxane and thelike, which have oxygen atom(s) in the ring; tetrahydrothiophene,tetrahydrothiopyrane having a sulfur atom in the ring; morpholine andthe like, which have a nitrogen atom and an oxygen atom in the ring; andthiomorpholine and the like, which have a nitrogen atom and a sulfuratom in the ring. They can be fused with a benzene ring and the like toform fused polycyclic heterocycles such as 2,3-dihydroindole,benzodioxane, 1,3-dihydroisobenzofuran, tetrahydroquinoline andtetrahydroisoquinoline.

Specific examples of unsaturated monocyclic heterocycles are pyridine,pyrimidine, pyrrole, imidazole, pyrazole, triazine and the like, whichhave nitrogen atom(s) in the ring; furan and the like, which have anoxygen atom in the ring; thiophene and the like, which have a sulfuratom in the ring; oxazole and the like, which have a nitrogen atom andan oxygen atom in the ring; and thiazole and the like, which have anitrogen atom and a sulfur atom in the ring. They can be fused with abenzene ring and the like to form fused polycyclic heterocycles such asindole, indazole, quinoline, isoquinoline, phenanthridine, benzofuran,benzimidazole, benzotriazole, benzoxazole, benzisoxazole andbenzothiazole.

The alkylamino is mono- or di-alkylamino. Specific examples ofalkylamino are methylamino, ethylamino and the like, which aremonoalkylamino; and dimethylamino, diethylamino, ethylmethylamino andthe like, which are dialkylamino.

The arylamino is mono- or di-arylamino. Specific examples of arylaminoare phenylamino, naphthylamino, methylphenylamino and the like, whichare monoarylamino; and diphenylamino, naphthylphenylamino and the like,which are diarylamino.

The acyl is hydrocarbonyl, alkylcarbonyl, cycloalkylcarbonyl,arylcarbonyl or heterocyclecarbonyl. Specific examples of acyl areformyl, which is hydrocarbonyl; acetyl, propionyl, butyryl, isobutyryl,valeryl, isovaleryl, pivaloyl, monochloroacetyl, trifluoroacetyl and thelike, which are alkylcarbonyl; cyclopentylcarbonyl, cyclohexylcarbonyland the like, which are cycloalkylcarbonyl; benzoyl, naphthoyl, toluoyland the like, which are arylcarbonyl; and furoyl, thenoyl, picolinoyl,nicotinoyl, isonicotinoyl and the like, which are heterocyclecarbonyl.

The halogen is fluorine, chlorine, bromine or iodine.

The alkylthio is straight-chain or branched alkylthio having one toeight carbon atoms. Specific examples of alkylthio are methylthio,ethylthio, n-propylthio, n-butylthio, n-pentylthio, n-hexylthio,n-heptylthio, n-octylthio, isopropylthio, isobutylthio, sec-butylthio,tert-butylthio, isopentylthio and the like.

Arylthio is monocyclic or fused polycyclic aromatic hydrocarbonthiohaving 6 to 14 carbon atoms or fused polycyclic hydrocarbonthio formedby condensation with a cycloalkane ring. Specific examples of arylthioare phenylthio and the like, which are monocyclic aromatichydrocarbonthio; naphthylthio, anthrylthio, phenanthrylthio and thelike, which are fused polycyclic aromatic hydrocarbonthio; andindanylthio, tetrahydronaphthylthio, tetrahydroanthrylthio and the like,which are fused polycyclic hydrocarbonthio.

Alkenyl is straight-chain or branched alkenyl having 2 to 8 carbonatoms. Specific examples of alkenyl are vinyl, allyl, propenyl, butenyl,pentenyl, hexenyl, heptenyl, octenyl, sec-butenyl, tert-pentenyl and thelike.

Alkynyl is straight-chain or branched alkynyl having 2 to 8 carbonatoms. Specific examples of alkynyl are ethynyl, propynyl, butynyl,pentynyl, hexynyl, heptynyl, octynyl, sec-butynyl, tert-pentynyl and thelike.

The ester of carboxyl is an ester with alkyl alcohol, aryl alcohol orthe like.

Specific examples of alkyl alcohol are methanol, ethanol, propanol,butanol, benzyl alcohol, phenethyl alcohol and the like, and specificexamples of aryl alcohol are phenol, naphthol, anthrol, cresol, xylenoland the like.

The amide of carboxyl is amide with alkylamine, cycloalkylamine,arylamine, heterocycleamine or the like.

Specific examples of alkylamine are methylamine, ethylamine,ethylmethyamine, dimethylamine, diethylamine, benzylamine and the like,specific examples of cycloalkylamine are cyclohexylamine,cyclohexylmethylamine and the like, specific examples of arylamine areaniline, naphthylamine, diphenylamine, ethylphenylamine, anisidine,toluidine and the like, and specific examples of heterocycleamine arebenzofuranylamine, quinolylamine and the like.

Sulfonyl is alkylsulfonyl or arylsulfonyl. Specific examples of sulfonylare methanesulfonyl, ethanesulfonyl and the like, which arealkylsulfonyl; and benzenesulfonyl, toluenesulfonyl and the like, whichare arylsulfonyl.

The substituted alkoxy is alkoxy having one or plural groups assubstituent(s) selected from halogen, hydroxy, alkoxy, alkoxysubstituted by aryl, aryloxy, cycloalkyl, aryl, aryl substituted byalkoxy, heterocycles, amino, alkylamino, arylamino, mercapto, alkylthio,arylthio, carboxyl or ester thereof or amide thereof, cyano and nitro.

The substituted aryloxy is aryloxy having one or plural groups assubstituent(s) selected from halogen, hydroxy, alkoxy, aryloxy, alkyl,cycloalkyl, aryl, heterocycles, amino, alkylamino, arylamino, mercapto,alkylthio, arylthio, carboxyl or ester thereof or amide thereof, formyl,alkylcarbonyl, arylcarbonyl, cyano and nitro.

The substituted alkyl is alkyl having one or plural groups assubstituent(s) selected from halogen, hydroxy, alkoxy, aryloxy,cycloalkyl, alkenyl, aryl, aryl substituted by halogen, aryl substitutedby alkoxy, heterocycles, amino, alkylamino, arylamino, mercapto,alkylthio, arylthio, carboxyl or ester thereof or amide thereof, formyl,alkylcarbonyl, arylcarbonyl, cyano and nitro.

The substituted cycloalkyl is cycloalkyl having one or plural groups assubstituent(s) selected from halogen, hydroxy, alkoxy, aryloxy, alkyl,cycloalkyl, aryl, heterocycles, amino, alkylamino, arylamino, mercapto,alkylthio, arylthio, carboxyl or ester thereof or amide thereof, formyl,alkylcarbonyl, arylcarbonyl, cyano and nitro.

The substituted aryl is aryl having one or plural groups assubstituent(s) selected from halogen, hydroxy, alkoxy, alkoxysubstituted by halogen, alkoxy substituted by aryl, aryloxy, alkyl,alkyl substituted by halogen, alkyl substituted by hydroxy, alkylsubstituted by ester of carboxyl, alkyl substituted by cyano,cycloalkyl, alkenyl, alkynyl, aryl, heterocycles, amino, alkylamino,arylamino, amino substituted by alkylsulfonyl, amino substituted byacyl, mercapto, alkylthio, alkylthio substituted by halogen, arylthio,carboxyl or ester thereof or amide thereof, carbonyl (i.e. oxo), formyl,alkylcarbonyl, arylcarbonyl, thiocarbonyl (i.e. thioxo), cyano, nitro,sulfonic group, alkylsulfonyl, alkylsulfonyl substituted by halogen andarylsulfonyl.

The substituted heterocycle is a heterocycle having one or plural groupsas substituent(s) selected from halogen, hydroxy, alkoxy, alkoxysubstituted by halogen, aryloxy, alkyl, alkyl substituted by halogen,alkyl substituted by hydroxy, alkyl substituted by carboxyl or esterthereof, cycloalkyl, aryl, heterocycles, amino, alkylamino, arylamino,amino substituted by acyl, mercapto, alkylthio, arylthio, carboxyl orester thereof or amide thereof, carbonyl (i.e. oxo), formyl,alkylcarbonyl, arylcarbonyl, thiocarbonyl (i.e. thioxo), cyano andnitro.

The substituted alkylamino is amino having one or plural groups in itsalkyl moiety as substituent(s) selected from halogen, hydroxy, alkoxy,aryloxy, cycloalkyl, aryl, heterocycles, amino, alkylamino, arylamino,mercapto, alkylthio, arylthio, carboxy or ester thereof or amidethereof, alkylcarbonyl, arylcarbonyl, cyano and nitro.

The substituted arylamino is amino having one or plural groups in itsaryl moiety as substituent(s) selected from halogen, hydroxy, alkoxy,aryloxy, alkyl, cycloalkyl, aryl, heterocycles, amino, alkylamino,arylamino, mercapto, alkylthio, arylthio, carboxyl or ester thereof oramide thereof, alkylcarbonyl, arylcarbonyl, cyano and nitro.

The substituted acyl is acyl having one or plural groups assubstituent(s) selected from halogen, hydroxy; alkoxy, aryloxy,cycloalkyl, aryl, heterocycles, amino, alkylamino, arylamino, mercapto,alkylthio, arylthio, carboxy or ester thereof or amide thereof,alkylcarbonyl, arylcarbonyl, cyano and nitro.

The substituted alkylthio is alkylthio having one or plural groups assubstituent(s) selected from halogen, hydroxy, alkoxy, aryloxy,cycloalkyl, aryl, heterocycles, amino, alkylamino, arylamino, carboxylor ester thereof or amide thereof, alkylcarbonyl, arylcarbonyl, cyanoand nitro.

The substituted arylthio is arylthio having one or plural groups assubstituent(s) selected from halogen, hydroxy, alkoxy, aryloxy, alkyl,cycloalkyl, aryl, heterocycles, amino, alkylamino, arylamino, carboxylor ester thereof or amide thereof, alkylcarbonyl, arylcarbonyl, cyanoand nitro.

When the present compound has free hydroxy, amino, alkylamino, arylaminoor mercapto as a substituent, these substituents can be protected with aprotecting group. When the heterocycle has a nitrogen atom, the nitrogenatom can be protected with a protecting group, too.

The protecting group of hydroxy is exemplified by widely-used protectinggroups such as unsubstituted alkenyl such as allyl; unsubstitutedheterocycles such as tetrahydropyranyl and tetrahydrofuranyl; esterssuch as methoxycarbonyl, ethoxycarbonyl, isobutoxycarbonyl,tert-butoxycarbonyl, vinyloxycarbonyl, allyloxycarbonyl,benzyloxycarbonyl and p-methoxybenzyloxycarbonyl; and substituted silylsuch as trimethylsilyl, triethylsilyl, triisopropylsilyl,tert-butyldimethylsilyl or tert-butyldiphenylsilyl.

The protecting group of a nitrogen atom of amino, alkylamino, arylaminoand heterocycles having a nitrogen atom in the ring is exemplified bywidely-used protecting groups such as unsubstituted alkenyl such asallyl; substituted acyl such as trichloroacetyl or trifluoroacetyl;unsubstituted acyl such as formyl, acetyl, benzoyl or picolinoyl; esterssuch as methoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl,2,2,2-trichloroethoxycarbonyl, benzyloxycarbonyl,

diphenylmethoxycarbonyl and phenoxycarbonyl; substituted sulfonyl suchas toluene sulfonyl or 2,4,6-trimethylbenzenesulfonyl; and unsubstitutedsulfonyl such as methanesulfonyl or benzenesulfonyl.

The protecting group of mercapto is exemplified by widely-usedprotecting groups such as unsubstituted alkenyl such as allyl;unsubstituted heterocycles such as tetrahydropyranyl andtetrahydrofuranyl; and esters such as methoxycarbonyl, ethoxycarbonyl,isobutoxycarbonyl, tert-butoxycarbonyl, vinyloxycarbonyl,allyoxycarbonyl, benzyloxycarbonyl and p-methoxybenzyloxycarbonyl.

The “salts” in the present compound can be any pharmaceuticallyacceptable salts and are exemplified by salts with an inorganic acidsuch as hydrochloric acid, hydrobromic acid, hydroiodic acid, nitricacid, sulfuric acid or phosphoric acid; salts with an organic acid suchas acetic acid, fumalic acid, maleic acid, succinic acid, citric acid,tartaric acid, adipic acid, lactic acid, methane sulfonic acid,trifluoromethanesulfonic acid or p-toluenesulfonic acid; salts with analkali metal such as lithium, sodium or potassium; salts with analkaline earth metal such as calcium or magnesium; and quaternary saltswith ammonia, methyl iodide or the like.

When there are geometrical isomers or optical isomers in the presentcompound, these isomers are also included in the present invention.

Further, the present compound can be in the form of a hydrate or asolvate.

-   (1) Preferred examples of the present compound are the following i)    to iii).-   i) Compounds wherein the ring “A” is a benzene ring in the general    formula [I]-   ii) Compounds wherein the ring “A” is selected from a pyrrole ring,    a pyrazole ring, an imidazole ring, a [1,2,3]triazole ring, a furan    ring, a thiophene ring, an oxazole ring, an isoxazole ring, a    thiazole ring, an isothiazole ring, a tetrahydroindole ring, a    tetrahydrobenzofuran ring and a tetrahydrobenzo[b]thiophene ring in    the general formula [I]. The ring “A” is more preferably a pyrazole    ring, a furan ring, a thiophene ring or tetrahydrobenzo[b]thiophene,    particularly a thiophene ring.-   iii) Compounds wherein the ring “A” is selected from a pyridine    ring, a pyridazine ring, a pyrimidine ring, a pyrazine ring, a    [1,2,3]triazine ring, a [1,2,4]triazine ring, a [1,2,3,4]tetrazine    ring, a tetrahydroquinoline ring, a tetrahydroisoquinoline ring, a    tetrahydroquinoxaline ring and a tetrahydrocinnoline ring in the    general formula [I]. The ring “A” is more preferably a pyridine ring    or a pyrazine ring, particularly preferably a pyridine ring.-   (2) More preferred examples of the present compounds are compounds    which satisfy the above-mentioned definitions (1) i) to iii) and    wherein a partial structure [C]

and a partial structure [D] in the general formula [I]

are bonded to adjacent carbon atoms on the ring “A”.

-   (3) Further preferred examples of the present compound are compounds    which satisfy the above-mentioned definitions (1) and (2) and    wherein the partial structure [C] or the partial structure [D] is    bonded to a carbon atom existing at the α-position of a heteroatom    of the ring “A”.-   (4) Preferred examples of respective substituents in the present    compound are as follows;

in the general formula [I],

-   a) R¹ and R², the same or different, are hydrogen, substituted or    unsubstituted alkoxy, substituted or unsubstituted alkyl,    substituted or unsubstituted cycloalkyl, substituted or    unsubstituted aryl, substituted or unsubstituted heterocycles,    substituted or unsubstituted alkylamino or substituted or    unsubstituted arylamino,-   b) alternatively, R¹ and R² join together to form a substituted or    unsubstituted heterocycle,-   c) X and Y are one or plural groups selected from hydrogen, halogen,    substituted or unsubstituted alkoxy, substituted or unsubstituted    alkyl, substituted or unsubstituted alkylthio, carboxyl or ester    thereof or amide thereof and cyano,-   d) p is 0 or 1.

Of course, the above-mentioned choices defined in a) to d) can bearbitrarily combined.

-   (5) More preferred examples of respective substituents in the    present compound are as follows;

in the general formula [I],

-   a) R¹ is hydrogen, substituted alkoxy, substituted or unsubstituted    alkyl, unsubstituted cycloalkyl, substituted or unsubstituted aryl,    a substituted or unsubstituted heterocycle, unsubstituted alkylamino    or substituted arylamino,-   b) R² is hydrogen or substituted or unsubstituted alkyl,-   c) alternatively, R¹ and R² join together to form a substituted or    unsubstituted heterocycle,-   d) X is one or plural groups selected from hydrogen, halogen and    substituted alkyl,-   e) Y is one or plural groups selected from hydrogen, halogen,    substituted or unsubstituted alkoxy, unsubstituted alkyl,    unsubstituted alkylthio, carboxyl or ester thereof or amide thereof    and cyano.

Of course, the above-mentioned choices defined in a) to e) can bearbitrarily combined.

Particularly preferred specific examples in the present invention areshown below.

-   N-(4-Chlorophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   2-(4-Pyridylmethylthio)-N-(3-quinolyl)pyridine-3-carboxamide

-   2-(4-Pyridylmethylthio)-N-(6-quinolyl)pyridine-3-carboxamide

-   N-(3-Isoquinolyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   N-(Indazol-5-yl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   N-Phenyl-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   N-(3-Isopropylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   N-(3-Chlorophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   2-(4-Pyridylmethylthio)-N-(3-trifluoromethoxyphenyl)pyridine-3-carboxamide

-   N-(4-Methylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   2-(4-Pyridylmethylthio)-N-(4-trifluoromethylphenyl)pyridine-3-carboxamide

-   N-(4-n-Propylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   N-(4-n-Butylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   N-(4-tert-Butylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   2-(4-Pyridylmethylthio)-N-(4-trifluoromethoxyphenyl)pyridine-3-carboxamide

-   N-(4-Isopropoxyphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   N-(4-Ethoxycarbonylmethylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   N-(4-Dimethylaminophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   N-(3-Methylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   N-(4-Chloro-2-fluorophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   N-(2,4-Difluorophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   N-(3,4-Dimethoxyphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   N-(4-Chloro-3-trifluoromethylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   N-(3-Chloro-4-fluorophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   N-(4-Fluoro-3-trifluoromethylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   N-(3-Chloro-4-methylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   N-(4-Chloro-3-methylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   N-(3,4-Dimethylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   N-(3-Fluoro-5-trifluoromethylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   N-(3,5-Dichlorophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   N-(5-Chloro-2,4-dimethoxyphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   N-(4-Chlorophenyl)-2-(4-pyridylmethylthio)benzamide

-   N-(3-Chlorophenyl)-2-(4-pyridylmethylthio)benzamide

-   N-(4-Dimethylaminophenyl)-2-(4-pyridylmethylthio)benzamide

-   N-(3-Isopropylphenyl)-2-(4-pyridylmethylthio)benzamide

-   N-(3,4-Dimethoxyphenyl)-2-(4-pyridylmethylthio)benzamide

-   2-(4-Pyridylmethylthio)-N-(3-quinolyl)benzamide

-   N-(4-Chlorophenyl)-5-fluoro-2-(4-pyridylmethylthio)benzamide

-   N-(4-Chloro-3-methylphenyl)-2-(4-pyridylmethylthio)benzamide

-   N-(5-Chloro-2,4-dimethoxyphenyl)-2-(4-pyridylmethylthio)benzamide

-   N-(3,5-Dimethylphenyl)-2-(4-pyridylmethylthio)benzamide

-   N-(3,5-Dimethylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   N-(4-Bromo-3-methylphenyl)-2-(4-pyridylmethylthio)benzamide

-   N-(5-Indanyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   N-(3-Chloro-4-trifluoromethoxyphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   2-(4-Pyridylmethylthio)-N-(4-trifluoromethylthiophenyl)pyridine-3-carboxamide

-   N-(3-Methyl-4-trifluoromethoxyphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   N-(3-Isoquinolyl)-2-(4-pyridylmethylthio)benzamide

-   N-(3,5-Dimethylphenyl)-2-(2-fluoropyridin-4-ylmethylthio)pyridine-3-carboxamide

-   2-(2-Fluoropyridin-4-ylmethylthio)-N-(4-trifluoromethoxyphenyl)-pyridine-3-carboxamide

-   2-(2-Fluoropyridin-4-ylmethylthio)-N-(5-indanyl)pyridine-3-carboxamide

-   2-(2-Chloropyridin-4-ylmethylthio)-N-(5-indanyl)pyridine-3-carboxamide

-   2-(2-Chloropyridin-4-ylmethylthio)-N-(3,5-dimethylphenyl)pyridine-3-carboxamide

-   2-(2-Chloropyridin-4-ylmethylthio)-N-(4-trifluoromethoxyphenyl)-pyridine-3-carboxamide

-   2-(3-Chloropyridin-4-ylmethylthio)-N-(3,5-dimethylphenyl)pyridine-3-carboxamide

-   2-(2-Bromopyridin-4-ylmethylthio)-N-(3,5-dimethylphenyl)pyridine-3-carboxamide

-   N-(3,5-Dimethylphenyl)-2-(2-methylthiopyridin-4-ylmethylthio)pyridine-3-carboxamide

-   N-(4-Chlorophenyl)-2-(2-methylthiopyridin-4-ylmethylthio)pyridine-3-carboxamide

-   2-(2-Cyanopyridin-4-ylmethylthio)-N-(3,5-dimethylphenyl)pyridine-3-carboxamide

-   2-(2-Ethoxycarbonylpyridin-4-ylmethylthio)-N-(3,5-dimethylphenyl)-pyridine-3-carboxamide

-   N-(4-Isopropoxyphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide

-   N-(3-Fluoro-4-methylphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide

-   N-(3-Chlorophenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide

-   N-(4-Chlorophenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide

-   3-(2-Chloropyridin-4-ylmethylthio)-N-(3,5-dimethylphenyl)thiophene-2-carboxamide

-   N-(4-Fluoro-3-methylphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide

-   N-(3,4-Dimethylphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide

-   3-(4-Pyridylmethylthio)-N-(4-trifluoromethylphenyl)thiophene-2-carboxamide

-   N-(4-tert-Butylphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide

-   N-(3-Methylphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide

-   N-(3,4-Difluorophenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide

-   N-(4-n-Propylphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide

-   3-(4-Pyridylmethylthio)-N-(4-trifluoromethoxyphenyl)thiophene-2-carboxamide

-   N-(3-Isoquinolyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide

-   N-(3,5-Dimethylphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide

-   3-(4-Pyridylmethylthio)-N-(3-trifluoromethylphenyl)thiophene-2-carboxamide

-   N-(5-Indanyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide

-   N-(4-Chlorophenyl)-2-(4-pyridylmethylthio)thiophene-3-carboxamide

-   N-(3-Methylphenyl)-2-(4-pyridylmethylthio)thiophene-3-carboxamide

-   N-(5-Indanyl)-2-(4-pyridylmethylthio)thiophene-3-carboxamide

-   N-(4-Bromo-3-methylphenyl)-2-(4-pyridylmethylthio)thiophene-3-carboxamide

-   2-(4-Pyridylmethylthio)-N-(4-trifluoromethylphenyl)thiophene-3-carboxamide

-   N-(3,5-Dimethylphenyl)-2-(4-pyridylmethylthio)thiophene-3-carboxamide

-   N-(3-Methylphenyl)-4-(4-pyridylmethylthio)thiophene-3-carboxamide

-   N-(Indazol-6-yl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide

-   2-(2-Bromopyridin-4-ylmethylthio)-N-(4-trifluoromethoxyphenyl)-pyridine-3-carboxamide

-   N-(3,5-Dimethylphenyl)-2-(2-methoxypyridin-4-ylmethylthio)pyridine-3-carboxamide

-   N-(3,5-Dimethylphenyl)-2-(2-methylpyridin-4-ylmethylthio)pyridine-3-carboxamide

-   2-(2-Methylpyridin-4-ylmethylthio)-N-(4-trifluoromethoxyphenyl)-pyridine-3-carboxamide

-   N-(4-Chlorophenyl)-2-(1-oxopyridin-4-ylmethylthio)pyridine-3-carboxamide

-   N-(3-Methylphenyl)-2-(1-oxopyridin-4-ylmethylthio)pyridine-3-carboxamide

-   N-(3,5-Dimethylphenyl)-2-(1-oxopyridin-4-ylmethylthio)pyridine-3-carboxamide

-   N-(3,4-Dimethylphenyl)-2-(1-oxopyridin-4-ylmethylthio)pyridine-3-carboxamide

-   N-(3-Isopropylphenyl)-2-(1-oxopyridin-4-ylmethylthio)pyridine-3-carboxamide

-   N-(4-Fluoro-3-methylphenyl)-2-(1-oxopyridin-4-ylmethylthio)pyridine-3-carboxamide

-   N-(5-Indanyl)-2-(1-oxopyridin-4-ylmethylthio)pyridine-3-carboxamide

-   2-(1-Oxopyridin-4-ylmethylthio)-N-(4-trifluoromethoxyphenyl)pyridine-3-carboxamide

-   N-(4-tert-Butylphenyl)-2-(1-oxopyridin-4-ylmethylthio)pyridine-3-carboxamide

-   N-(3-Chloro-4-trifluoromethoxyphenyl)-2-(1-oxopyridin-4-ylmethylthio)-pyridine-3-carboxamide

-   N-(3-Chlorophenyl)-2-[1-(4-pyridyl)ethythio]pyridine-3-carboxamide

-   2-(2-Carboxypyridin-4-ylmethylthio)-N-(3,5-dimethylphenyl)pyridine-3-carboxamide

-   N-(3,5-Dimethylphenyl)-2-(2-n-propylaminocarbonylpyridin-4-yl-methylthio)pyridine-3-carboxamide

-   2-[2-(4-Chlorophenylaminocarbonyl)pyridin-4-ylmethylthio]-N-(3,5-dimethylphenyl)pyridine-3-carboxamide

-   N-(3,5-Dimethylphenyl)-2-(2-methylaminocarbonylpyridin-4-yl-methylthio)pyridine-3-carboxamide

-   N-(3,5-Dimethylphenyl)-2-[2-(2-methoxyethylaminocarbonyl)pyridine-4-ylmethylthio]pyridine-3-carboxamide

-   2-(2-Carbamoylpyridin-4-ylmethylthio)-N-(3,5-dimethylphenyl)pyridine-3-carboxamide

The compounds of the present invention can be prepared according to thefollowing methods. Each specific process for preparing the presentcompounds will be described in detail in later Examples (section ofPreparation). The term “Hal” used in the following synthetic routesrepresents a halogen atom.

The processes for preparing the compounds of the present invention aredivided roughly into the methods 1˜4) described below, and the suitablemethod can be chosen according to the kind of substituent.

1) The compound of the present invention (Ia, p=0) can be synthesizedaccording to Synthetic route 1. Namely, the compound of this invention(Ia) can be given by the reaction of compound (II) with amine (III) inan organic solvent such as methylene chloride or N,N-dimethylformamide(DMF) in the presence of a condensing agent such asN,N′-dicyclohexylcarbodiimide (DCC) orO-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluroniumhexafluoro-phosphate (HATU) or N-benzyl-N′-cyclohexylcarbodiimidepolymer-bound, and in the presence of a base such asN,N-diisopropylethylamine at room temperature to 50° C. for 1 hour to 12hours.

Synthetic Route 1

Compound (II) can be synthesized according to Synthetic route 1-1.Namely, compound (II) can be given by the reaction of compound (IV) withcompound (Va) or compound (Vb) in an organic solvent such as DMF in thepresence of a base such as triethylamine at 0° C. to room temperaturefor 1 hour to 12 hours.

Synthetic Route 1-1

Compound (II) can also be synthesized according to Synthetic route 1-2.Namely, compound (II) can be given by the treatment of compound (VI) inan organic solvent such as methanol in the presence of a 1N aqueoussodium hydroxide solution at room temperature to 50° C. for 1 hour to 12hours.

Synthetic Route 1-2

Compound (Va, q=0) can be synthesized according to Synthetic route 1-3.Namely, compound (Va) can be given by the treatment of compound (VII) inan organic solvent such as methylene chloride in the presence of ahalogenating agent such as carbon tetrabromide-triphenylphosphine at 0°C. to room temperature for 1 hour to 4 hours.

Synthetic Route 1-3

Compound (Vb, q=1) can be synthesized according to Synthetic route 1-4.Namely, compound (Vb, q=1) whose nitrogen atom in a pyridine ring isoxidized can be given by the treatment of compound (Va, q=0) in anorganic solvent such as methylene chloride in the presence of anoxidizing agent such as m-chloroperbenzoic acid at 0° C. to roomtemperature for 1 hour to 24 hours.

Synthetic Route 1-4

Compound (VI) can be synthesized according to Synthetic route 1-5.Namely, compound (VI) can be given by the reaction of compound(VIII)with compound (IX) in an organic solvent such as N,N-dimethylacetamidein the presence of a transition metal catalyst such as palladium, and inthe presence of a catalytic ligand such as triphenylphosphine and a basesuch as N,N-diisopropylethylamine at 60° C. to 100° C. for 2 hours to 24hours.

Synthetic Route 1-5

2) The compound of the present invention (Ib, p=0) can be synthesizedaccording to Synthetic route 2. Namely, the compound of this invention(Ib) can be given by the reaction of compound (X) with compound (Va) or(Vb) in an organic solvent such as DMF in the presence of a base such astriethylamine at room temperature to 80° C. for 1 hour to 24 hours.

Synthetic Route 2

Compound (X) can be synthesized according to Synthetic route 2-1.Namely, compound (IV) is reacted with a halogenating agent such asthionyl chloride, in an organic solvent such as methylene chloride, andin the presence of a base such as pyridine at room temperature for 15minutes to 3 hours. The resulting acid chloride (XI) is reacted withamine (III) in an organic solvent such as chloroform in the presence ofa base such as pyridine at room temperature to 80° C. for 1 hour to 24hours to give compound (X).

Synthetic Route 2-1

3) The compound of this invention (Ic, p=0) can be synthesized accordingto Synthetic route 3. Namely, the compound of this invention (Ic) can bealso given by the reaction of compound (XII) with compound (IX) in anorganic solvent such as DMF in the presence of a base such as potassiumcarbonate at 40° C. to 80° C. for 1 hour to 12 hours. It is also givenby the reaction of compound (XII) with compound (IX) in an organicsolvent such as N,N-dimethylacetamide in the presence of a transitionmetal catalyst such as palladium, a catalytic ligand such astriphenylphosphine and a base such as N,N-diisopropylethylamine at 60°C. to 100° C. for 2 hours to 24 hours.

Synthetic Route 3

Compound (XII) can be synthesized according to Synthetic route 3-1.Namely, compound (XII) can be given by the reaction of compound (XIII)with amine (III) in an organic solvent such as tetrahydrofuran or DMF inthe presence of a base such as N,N-diisopropylethylamine at 0° C. to 50°C. for 1 hour to 12 hours.

Synthetic Route 3-1

4) The compound of the present invention (Id, p=1 or 2) can also besynthesized according to Synthetic route 4. Namely, the compound of thisinvention(Id), wherein the sulfur atom of compound (Ia, Ib or Ic) isoxidized, can be given by the treatment of this compound (Ia, Ib or Ic)in an organic solvent such as chloroform in the presence of an oxidizingagent such as m-chloroperbenzoic acid or hydrogen peroxide at 0° C. toroom temperature for 1 hour to 12 hours.

Synthetic Route 4

The compound of the present invention prepared by the above syntheticroutes can be converted into the above-mentioned salts, hydrates orsolvates using widely-used techniques.

The present invention also relates to pharmaceutical compositionscomprising the present compound or the salt thereof and a pharmaceuticalcarrier.

The present invention further relates to a method of treating diseasesin which angiogenesis or augmentation of vascular permeability isinvolved comprising administering to patients a pharmaceuticallyeffective amount of the present compound or the salt thereof for thetreatment.

The following pharmacological tests 1 to 4 were carried out, andpharmacological effects of the present compounds were evaluated in orderto find utility of the present compounds. Details will be mentioned inExamples (under the item of pharmacological tests) later. The presentcompounds demonstrated excellent cell growth inhibitory actions in thepharmacological test 1 (in vitro), angiogenesis inhibitory effects werefound, and inhibition of augmentation of vascular permeability wassuggested. Further, the present compounds demonstrated excellent tumorgrowth inhibitory actions, paw edema inhibitory actions and choroidalneovascularization inhibitory effects in pharmacological tests 2 to 4(in vivo) using specific disease model animals, and it was found thatthe present compounds are useful as therapeutic agents for specificdiseases in which angiogenesis or augmentation of vascular permeabilityis involved.

1. Evaluation Tests of Angiogenesis Inhibitory Effects

Cell growth inhibitory action tests were carried out using aVEGF-induced HUVEC growth reaction evaluation system (HUVEC stands forhuman umbilical vein endothelial cells), which is one of widely-usedmethods of evaluating in vitro angiogenesis inhibitory effects of drugs.

2. Evaluation Tests of Anticancer Effects

Tumor proliferation inhibitory action tests of the present compoundswere carried out using a mouse cancer model, which is one of widely-usedmethods of evaluating in vivo anticancer effects of drugs.

3. Evaluation Tests of Antiarthritis Effects

Paw edema inhibitory action tests of the present compounds were carriedout using a rat adjuvant arthritis model, which is one of widely-usedmethods of evaluating in vivo antiarthritis effects of drugs.

4. Evaluation Tests of Choroidal Neovascularization Inhibitory Effects

Neovascularization incidence tests of the present compounds were carriedout using a rat choroidal neovascularization model, which is one ofwidely-used methods of evaluating in vivo choroidal neovascularizationinhibitory effects of drugs.

As shown in the tests 1 to 4, the present compounds are useful as atherapeutic agents for the diseases in which angiogenesis oraugmentation of vascular permeability is involved, specifically cancer,rheumatoid arthritis, age-related macular degeneration, diabeticretinopathy, retinopathy of prematurity, retinal vein occlusion,polypoid choroidal angiopathy, diabetic macular edema, psoriasisvulgaris and pultaceous arteriosclerosis.

The present compound can be administered orally or parenterally.Examples of dosage forms are a tablet, a capsule, granule, powder, aninjection, an ophthalmic solution and the like. The preparations can beprepared by the usual methods.

For example, oral preparations such as a tablet, a capsule, granule andpowder can be prepared by optionally adding an excipient such aslactose, mannitol, starch, crystalline cellulose, light silicicanhydride, calcium carbonate or calcium hydrogenphosphate, a lubricantsuch as stearic acid, magnesium stearate or talc, a binder such asstarch, hydroxypropylcellulose, hydroxypropylmethylcellulose orpolyvinylpyrrolidone, a disintegrator such as carboxymethylcellulose,low-substituted hydroxypropylmethylcellulose or calcium citrate, acoating agent such as hydroxypropylmethylcellulose, macrogol or asilicone resin, a stabilizer such as ethyl p-hydroxybenzoate or benzylalcohol, or corrigent such as a sweetening agent, a sour agent or aperfume.

Parenteral preparations such as an injection and an ophthalmic solutioncan be prepared by optionally adding a tonicity agent such as sodiumchloride, concentrated glycerin, propylene glycol, polyethylene glycol,potassium chloride, sorbitol or mannitol, a buffer such as sodiumphosphate, sodium hydrogenphosphate, sodium acetate, citric acid,glacial acetic acid or trometamol, a surfactant such as polyoxyethylenesorbitan monoolate, polyoxyl 40 stearate or polyoxyethylene hydrogenatedcastor oil, a stabilizer such as sodium citrate or disodium edetate, apreservative such as benzalkonium chloride, paraben, benzethoniumchloride, p-hydroxybenzoate, sodium benzoate or chlorobutanol, a pHadjusting agent such as hydrochloric acid, citric acid, phosphoric acid,acetic acid, sodium hydroxide, sodium carbonate or sodiumhydrogencarbonate or a soothing agent such as benzyl alcohol.

The dosage of the present compound can be appropriately selecteddepending on symptoms, age of patients, dosage form and the like. Forexample, in the case of oral preparations, the usually daily dosage is0.01 to 1,000 mg, preferably 1 to 100 mg of the present compound, whichcan be given in a single dose or several divided doses.

In the case of ophthalmic solutions, they can be instilled once toseveral times per day with a concentration of 0.0001 to 10% (w/v),preferably 0.01 to 5% (w/v).

Examples of preparations and formulations of the present compounds andresults of pharmacological tests are shown below. These examples do notlimit the scope of the present invention, but are intended to make thepresent invention more clearly understandable.

PREPARATION EXAMPLES Reference Example 12-(4-Pyridylmethylthio)pyridine-3-carboxylic acid (Reference compoundNo. 1-1)

2-Mercaptonicotinic acid (7.8 g, 50 mmol) and 4-(bromomethyl)pyridinehydrobromide (12.6 g, 50 mmol) were suspended in N,N-dimethylformamide(100 mL) under ice-cooling. Triethylamine (21 ml, 150 mmol) was addeddropwise to the suspension, and the whole was stirred at roomtemperature for 6 hours. Water (300 mL) was added to the reactionmixture, then the aqueous layer was washed with ethyl acetate (100 mL).2 N hydrochloric acid was added to the aqueous layer to adjust to pH 7,and the precipitated solid was filtered off. The solid was washed withwater and diethyl ether, and dried at 50° C. under reduced pressure togive 7.5 g of the title reference compound as a gray solid. (Yield 61%)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.38 (s, 2H), 7.27 (dd, J=8.1, 4.8 Hz, 1H), 7.42 (dd, J=4.4, 1.5 Hz,2H), 8.22 (dd, J=8.1, 1.8 Hz, 1H), 8.46 (dd, J=4.4, 1.5 Hz, 2H), 8.63(dd, J=4.8, 1.8 Hz, 1H), 13.70 (br s, 1H)

As described below, Reference compounds (No. 1-2˜11) were obtained by amethod similar to Reference Example 1.

2-(4-Pyridylmethylthio)benzoic acid (Reference compound No. 1-2)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.25 (s, 2H), 7.21 (td, J=7.5, 1.2 Hz, 1H), 7.40-7.51 (m, 4H), 7.88(dd, J=7.8, 1.8 Hz, 1H), 8.50 (dd, J=4.3, 1.5 Hz, 2H), 13.12 (br s, 1H)

5-Fluoro-2-(4-pyridylmethylthio)benzoic acid (Reference compound No.1-3)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.55 (s, 2H), 7.39 (td, J=8.0, 2.9 Hz, 1H), 7.49 (dd, J=9.0, 5.1 Hz,1H), 7.62 (dd, J=9.3, 2.9 Hz, 1H), 8.00 (d, J=6.6 Hz, 2H), 8.81 (d,J=6.6 Hz, 2H)

4-(4-Pyridylmethylthio)pyridine-3-carboxylic acid (Reference CompoundNo. 1-4)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.35 (s, 2H), 7.45 (d, J=5.6 Hz, 1H), 7.49 (d, J=6.1 Hz, 2H), 8.50 (d,J=5.6 Hz, 1H), 8.54 (d, J=6.1 Hz, 2H), 8.92 (s, 1H), 13.70 (br s, 1H)

3-(4-Pyridylmethylthio)pyridine-2-carboxylic acid (Reference CompoundNo. 1-5)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.30 (s, 2H), 7.42 (dd, J=4.4, 1.6 Hz, 2H), 7.50 (m, 1H), 7.92 (dd,J=8.3, 1.2 Hz, 1H), 8.40 (dd, J=4.6, 1.2 Hz, 1H), 8.50 (dd, J=4.4, 1.6Hz, 2H), 13.26 (br s, 1H)

2-(2,6-Dichloropyridin-4-ylmethylthio)pyridine-3-carboxylic acid(Reference compound No. 1-6)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.40 (s, 2H), 7.29 (dd, J=7.8, 4.7 Hz, 1H), 7.62 (s, 2H), 8.25 (dd,J=7.8, 1.7 Hz, 1H), 8.64 (dd, J=4.7, 1.7 Hz, 1H), 13.58 (s, 1H)

2-(2-Fluoropyridin-4-ylmethylthio)pyridine-3-carboxylic acid (Referencecompound No. 1-7)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.20 (s, 1H), 7.27 (dd, J=7.6, 4.7 Hz, 1H), 7.40 (m,1H), 8.13 (d, J=5.2 Hz, 1H), 8.23 (dd, J=7.6, 1.8 Hz, 1H), 8.64 (dd,J=4.7, 1.8 Hz, 1H), 13.49 (s, 1H)

2-(2-Bromopyridin-4-ylmethylthio)pyridine-3-carboxylic acid (Referencecompound No. 1-8)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.37 (s, 2H), 7.28 (dd, J=7.8, 4.7 Hz, 1H), 7.48 (dd, J=4.9, 1.4 Hz,1H), 7.69 (dd, J=1.4, 0.4 Hz, 1H), 8.23 (dd, J=7.8, 1.8 Hz, 1H), 8.27(dd, J=4.9, 0.4 Hz, 1H), 8.63 (dd, J=4.7, 1.8 Hz, 1H), 13.55 (s, 1H)

3-(4-Pyridylmethylthio)thiophene-2-carboxylic acid (Reference compoundNo. 1-9)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.35 (s, 2H), 7.19 (d, J=5.2 Hz, 1H), 7.45 (d, J=5.8 Hz, 2H), 7.84 (d,J=5.2 Hz, 1H), 8.51 (d, J=5.8 Hz, 2H), 13.06 (s, 1H)

3-(4-Pyridylmethylthio)benzoic acid (Reference compound No. 1-10)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.33 (s, 2H), 7.35 (dd, J=4.3, 1.5 Hz, 2H), 7.42 (m, 1H), 7.58 (ddd,J=7.8, 2.0, 1.0 Hz, 1H), 7.74 (m, 1H), 7.82 (t, J=7.8 Hz, 1H), 8.47 (dd,J=4.4, 1.7 Hz, 2H), 13.12 (s, 1H)

4-(4-Pyridylmethylthio)benzoic acid (Reference compound No. 1-11)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.38 (s, 2H), 7.42 (m, 4H), 7.82 (dt, J=8.6, 1.8 Hz, 2H), 8.50 (dd,J=4.4, 1.7 Hz, 2H), 12.92 (s, 1H)

Reference Example 2 2-Chloro-N-(4-chlorophenyl)pyridine-3-carboxamide(Reference compound No. 2-1)

2-Chloronicotinoyl chloride (4.0 g, 23 mmol) was added to a solution of4-chloroaniline (3.2 g, 25 mmol) and N,N-diisopropylethylamine (7.7 mL,46 mmol) in tetrahydrofuran (40 mL), and then the mixture was stirred atroom temperature for 3 hours. Ethyl acetate (150 mL) was added to thereaction mixture, and the ethyl acetate layer was washed with asaturated aqueous sodium hydrogencarbonate solution (100 mL) twice andbrine (100 mL) twice. The ethyl acetate layer was dried over anhydrousmagnesium sulfate, the solvent was evaporated under reduced pressure,and the precipitated solid was filtered off. The solid was washed withdiethyl ether:ethyl acetate (3:1), and then dried under reduced pressureto give 4.2 g of the title reference compound as a white solid. (Yield82%)

¹H-NMR (400 MHz, CDCl₃)

δ 7.36 (d, J=8.9 Hz, 2H), 7.42 (dd, J=7.7, 4.8 Hz, 1H), 7.61 (d, J=8.9Hz, 2H), 8.22 (s, 1H), 8.23 (dd, J=7.7, 1.9 Hz, 1H), 8.53 (dd, J=4.8,1.9 Hz, 1H)

As described below, Reference compounds (No. 2-2-7) were obtained by themethod similar to Reference Example 2.

2-Chloro-N-(4-trifluoromethylsulfonylphenyl)pyridine-3-carboxamide(Reference compound No. 2-2)

-   ¹H-NMR (400 MHz, DMSO-d₆)

δ 7.62 (dd, J=7.6, 4.9 Hz, 1H), 8.11-8.18 (m, 5H), 8.59 (dd, J=4.9, 2.0Hz, 1H), 11.41 (s, 1H)

N-(3-Fluoro-5-trifluoromethylphenyl)-2-iodobenzamide (Reference compoundNo. 2-3)

¹H-NMR (500 MHz, DMSO-d₆)

δ 7.27 (m, 1H), 7.52 (dd, J=9.7, 1.7 Hz, 1H), 7.53-7.55 (m, 2H), 7.87(d, J=1.0 Hz, 1H), 7.96 (s, 1H), 7.97 (d, J=7.8 Hz, 1H), 10.96 (s, 1H)

5-Bromo-N-(4-chlorophenyl)furan-2-carboxamide (Reference compound No.2-4)

¹H-NMR (500 MHz, DMSO-d₆)

δ 6.84 (d, J=3.7 Hz, 1H), 7.38 (d, J=3.7 Hz, 1H), 7.41 (d, J=7.0 Hz,2H), 7.76 (d, J=7.0 Hz, 2H), 10.33 (s, 1H)

5-Bromo-N-(4-chlorophenyl)thiophene-2-carboxamide (Reference compoundNo. 2-5)

¹H-NMR (500 MHz, DMSO-d₆)

δ 7.38 (d, J=4.0 Hz, 1H), 7.42 (d, J=8.9 Hz, 2H), 7.73 (d, J=8.9 Hz,2H), 7.85 (d, J=4.0 Hz, 1H), 10.38 (s, 1H)

5-Bromo-N-(3,5-dimethylphenyl)furan-2-carboxamide (Reference compoundNo. 2-6)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.26 (s, 6H), 6.75 (d, J=0.7 Hz, 1H), 6.82 (d, J=3.7 Hz, 1H), 7.35 (d,J=0.7 Hz, 2H), 7.35 (d, J=3.7 Hz, 1H), 10.02 (s, 1H)

5-Bromo-N-(3,5-dimethylphenyl)thiophene-2-carboxamide (Referencecompound No. 2-7)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.26 (s, 6H), 6.76 (s, 1H), 7.33 (s, 2H), 7.36 (d, J=4.0 Hz, 1H), 7.85(d, J=4.0 Hz, 1H), 10.12 (s, 1H)

Reference Example 3 4-(Chloromethyl)pyridine-N-oxide (Reference compoundNo. 3-1)

A 2 N aqueous sodium hydroxide solution (10 mL) and water (20 mL) wereadded to 4-(chloromethyl)pyridine hydrochloride (1.6 g, 10 mmol), andthe reaction mixture was extracted with chloroform (20 mL) twice. Thechloroform layer was dried over anhydrous magnesium sulfate, and thenthe solvent was evaporated under reduced pressure. m-Chloroperoxybenzoicacid (65%, 5.3 g, 20 mmol) was added to a solution of the resultingresidue in dichloromethane (20 mL), and then the mixture was stirred atroom temperature for 17 hours. Chloroform (100 mL) and a saturatedaqueous sodium hydrogencarbonate solution (120 mL) were added to thereaction mixture, and then the chloroform layer was washed with asaturated aqueous sodium hydrogencarbonate solution (80 ml) and brine(100 mL). The chloroform layer was dried over anhydrous magnesiumsulfate, and then the solvent was evaporated under reduced pressure. Theresulting residue was purified by silica gel column chromatography togive 300 mg of the title reference compound as a brown solid. (Yield21%)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.77 (s, 2H), 7.47 (d, J=7.1 Hz, 2H), 8.22 (d, J=7.1 Hz, 2H)

Reference Example 4 2-(1-Oxopyridin-4-ylmethylthio)pyridine-3-carboxylicacid (Reference compound No. 4-1)

2-Mercaptonicotinic acid (270 mg, 1.7 mmol) and4-(chloromethyl)pyridine-N-oxide (260 mg, 1.7 mmol, Reference compoundNo. 3-1) were suspended in N,N-dimethylformamide (100 mL). Triethylamine(0.75 ml, 5.4 mmol) was added dropwise thereto, and the mixture wasstirred at room temperature for 7.5 hours. Water (30 mL) was added tothe reaction mixture, and the whole was washed with ethyl acetate (50mL). 1 N hydrochloric acid (5.0 ml) was added to the aqueous layer toadjust to pH 7, the precipitated solid was filtered off. The solid waswashed with water and diethyl ether, and then dried under reducedpressure to give 200 mg of the title reference compound as a pale redsolid. (Yield 47%)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.35 (s, 2H), 7.28 (dd, J=7.8, 4.8 Hz, 1H), 7.43 (d, J=7.1 Hz, 2H),8.11 (dd, J=5.1, 2.0 Hz, 2H), 8.23 (dd, J=7.8, 1.9 Hz, 1H), 8.64 (dd,J=4.8, 1.9 Hz, 1H), 13.50 (br, 1H)

Reference Example 5 2-[1-(4-Pyridyl)ethylthio]pyridine-3-carboxylic acid(Reference compound No. 5-1)

Triphenylphosphine (4.8 g, 18 mmol) and carbon tetrabromide (7.4 g, 22mmol) were added to a solution of (±)-1-(4-pyridyl)ethanol (1.9 g, 15mmol) in methylene chloride (75 mL) under ice-cooling, and then themixture was stirred at room temperature for 1 hour. A saturated aqueoussodium hydrogencarbonate solution (100 mL) was added to the reactionmixture, the whole was extracted with chloroform (60 mL), and then thechloroform layer was washed with brine (80 mL). The chloroform layer wasdried over anhydrous magnesium sulfate, and then the solvent wasevaporated under reduced pressure. The resulting residue was purified bysilica gel column chromatography to give (±)-1-(1-bromoethyl)pyridine(2.0 g, 72%). Immediately, triethylamine (3.1 mL, 22 mmol) was addeddropwise to a solution of this bromo intermediate (2.0 g, 11 mmol) and2-mercaptonicotinic acid (1.2 g, 7.8 mmol) in N,N-dimethylformamide (100mL) at room temperature, and the reaction mixture was stirred for 15hours. Water (50 mL) was added to the reaction mixture, the whole waswashed with ethyl acetate (50 mL), then the aqueous layer was adjustedto pH 7 with 1N hydrochloric acid and extracted with chloroform (50 mL).The chloroform layer was dried over anhydrous magnesium sulfate, andthen the solvent was evaporated under reduced pressure to give the titlereference compound including N,N-dimethylformamide.

¹H-NMR (400 MHz, DMSO-d₆)

δ 1.64 (d, J=7.1 Hz, 3H), 5.14 (q, J=7.1 Hz, 1H), 7.23 (dd, J=7.6, 4.7Hz, 1H), 7.48 (dd, J=4.5, 1.5 Hz, 2H), 8.19 (dd, J=7.6, 1.7 Hz, 1H),8.48 (dd, J=4.5, 1.5 Hz, 2H), 8.60 (dd, J=4.7, 1.7 Hz, 1H), 13.50 (br s,1H)

Reference Example 6 2-Methylthioisonicotinic acid methyl ester(Reference compound No. 6-1)

2-Chloroisonicotinic acid methyl ester (1.0 g, 60 mmol) and sodiumthiomethoxide (0.42 g, 60 mmol) were suspended in methanol (10 mL), andthe whole was refluxed under a nitrogen atmosphere for 3 hours. Thereaction mixture was diluted with ethyl acetate (60 mL) and washed witha saturated aqueous sodium hydrogencarbonate solution (100 mL) and brine(100 mL). The ethyl acetate layer was dried over anhydrous magnesiumsulfate, and then the solvent was evaporated under reduced pressure. Theresulting residue was purified by silica gel column chromatography togive 0.20 g of the title reference compound as a colorless oil. (Yield22%)

¹H-NMR (500 MHz, CDCl₃)

δ 2.60 (s, 3H), 3.94 (s, 3H), 7.49 (dd, J=5.2, 1.6 Hz, 1H), 7.73 (dd,J=1.6, 1.0 Hz, 1H), 8.56 (dd, J=5.2, 1.0 Hz, 1H)

Reference Example 7 2-Chloropyridine-4-methanol (Reference compound No.7-1)

A 0.95 M solution of diisobutylaluminum hydride in hexane (200 mL, 190mmol) was added dropwise to a solution of 2-chloroisonicotinic acidmethyl ester (11 g, 62 mmol) in anhydrous tetrahydrofuran (300 mL) undera nitrogen atmosphere under ice-cooling, and then the mixture wasstirred under ice-cooling for 2 hours. After that, 1 N hydrochloric acid(200 mL) was added thereto, the mixture was stirred at room temperaturefor 1 hour. A saturated aqueous sodium hydrogencarbonate solution (400mL) was added to the reaction mixture, then the whole was extracted withethyl acetate (100 mL) three times. The ethyl acetate layer was driedover anhydrous magnesium sulfate, and then the solvent was evaporatedunder reduced pressure to give 8.5 g of the title reference compound asa white solid. (Yield 95%)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.56 (d, J=5.8 Hz, 2H), 5.54 (t, J=5.8 Hz, 1H), 7.34 (d, J=4.9 Hz,1H), 7.41 (s, 1H), 8.34 (d, J=4.9 Hz, 1H)

As described below, Reference compounds (No. 7-2˜3) were obtained by amethod similar to Reference Example 7.

2-Methylthiopyridine-4-methanol (Reference compound No. 7-2)

¹H-NMR (500 MHz, CDCl₃)

δ 2.16 (br s, 1H), 2.56 (s, 3H), 4.68 (s, 2H), 6.95 (dt, J=5.1, 0.7 Hz,1H), 7.19 (dd, J=1.4, 0.7 Hz, 1H), 8.38 (d, J=5.1 Hz, 1H)

2-Methylpyridine-4-methanol (Reference compound No. 7-3)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.44 (s, 3H), 4.49 (d, J=5.5 Hz, 2H), 5.36 (t, J=5.5 Hz, 1H), 7.10 (d,J=5.1 Hz, 1H), 7.17 (s, 1H), 8.35 (d, J=5.1 Hz, 1H)

Reference Example 8 2-Methoxypyridine-4-methyl methoxymethyl ether(Reference compound No. 8-1)

Methanol (0.46 mL, 11 mmol) was added to the suspension of potassiumtert-butoxide (1.2 g, 11 mmol) in tetrahydrofuran (50 mL), then themixture was refluxed for 3 hours. A solution of2-chloropyridine-4-methyl methoxymethyl ether (1.0 g, 5.3 mmol) intetrahydrofuran (10 mL) was added to the reaction mixture, and themixture was refluxed for 3 hours. The mixture was allowed to stand anddiluted with ethyl acetate (100 mL), and then the ethyl acetate layerwas washed with water (200 mL) and brine (100 mL). The ethyl acetate wasdried over anhydrous magnesium sulfate, and then the solvent wasevaporated under reduced pressure. The resulting residue was purified bysilica gel column chromatography to give 0.89 g of the title referencecompound as a yellow oil. (Yield 91%)

¹H-NMR (500 MHz, CDCl₃)

δ 3.41 (s, 3H), 3.94 (s, 3H), 4.56 (s, 2H), 4.71 (s, 2H), 6.74 (s, 1H),6.85 (dd, J=5.2, 0.6 Hz, 1H), 8.12 (d, J=5.2 Hz, 1H)

As described below, Reference compounds (No. 8-2˜4) were obtained by amethod similar to Reference Example 8.

2-Ethoxypyridine-4-methyl methoxymethyl ether (Reference compound No.8-2)

¹H-NMR (500 MHz, CDCl₃)

δ 1.39 (t, J=7.0 Hz, 3H), 3.41 (s, 3H), 4.35 (q, J=7.0 Hz, 2H), 4.56 (s,2H), 4.71 (s, 2H), 6.73 (s, 1H), 6.82 (dd, J=5.2, 1.2 Hz, 1H), 8.10 (d,J=5.2 Hz, 1H)

2-Isopropoxypyridine-4-methyl methoxymethyl ether (Reference compoundNo. 8-3)

¹H-NMR (500 MHz, CDCl₃)

δ 1.34 (d, J=6.1 Hz, 6H), 3.41 (s, 3H), 4.54 (s, 2H), 4.71 (s, 2H), 5.30(m, 1H), 6.68 (s, 1H), 6.80 (dd, J=5.2, 1.2 Hz, 1H), 8.09 (d, J=5.2 Hz,1H)

2-Benzyloxypyridine-4-methyl methoxymethyl ether (Reference compound No.8-4)

¹H-NMR (400 MHz, CDCl₃)

δ 3.41 (s, 3H), 4.57 (s, 2H), 4.71 (s, 2H), 5.38 (s, 2H), 6.62 (dd,J=1.6, 1.0 Hz, 1H), 6.87 (dd, J=5.2, 0.6 Hz, 1H), 7.32 (d, J=7.3 Hz,1H), 7.37 (t, J=7.6 Hz, 2H), 7.45 (dd, J=7.6, 0.6 Hz, 2H), 8.13 (dd,J=5.2, 0.6 Hz, 1H)

Reference Example 9 2-Methoxypyridine-4-methanol (Reference compound No.9-1)

A solution of 4 N hydrogen chloride in ethyl acetate (11 mL, 44 mmol)was added to 2-methoxypyridine-4-methyl methoxymethyl ether (0.77 g, 4.2mmol, Reference compound No. 8-1) under ice-cooling, then the mixturewas stirred for 30 minutes. The mixture was diluted with chloroform (100mL) and washed with a saturated aqueous sodium hydrogencarbonatesolution (50 mL) twice. The chloroform layer was dried over anhydrousmagnesium sulfate, then the solvent was evaporated under reducedpressure to give 0.69 g of the title reference compound as a yellow oil.(Yield 99%)

¹H-NMR (500 MHz, CDCl₃)

δ 1.89 (s, 1H), 3.94 (s, 3H), 4.69 (d, J=4.3 Hz, 2H), 6.75 (s, 1H), 6.85(d, J=5.2 Hz, 1H), 8.12 (d, J=5.2 Hz, 1H)

As described below, Reference compounds (No. 9-2˜4) were obtained by amethod similar to Reference Example 9.

2-Ethoxypyridine-4-methanol (Reference compound No. 9-2)

¹H-NMR (400 MHz, CDCl₃)

δ 1.39 (t, J=7.1 Hz, 3H), 2.32 (br s, 1H) 4.34 (q, J=7.1 Hz, 2H), 4.67(s, 2H), 6.73 (dd, J=1.5, 1.0 Hz, 1H), 6.82 (dd, J=5.4, 1.0 Hz, 1H),8.08 (d, J=5.4 Hz, 1H)

2-Isopropoxypyridine-4-methanol (Reference compound No. 9-3)

¹H-NMR (400 MHz, CDCl₃)

δ 1.34 (d, J=6.5 Hz, 6H), 1.78 (br sJH), 4.71 (s, 2H), 5.30 (m, 1H),6.69 (s, 1H), 6.81 (d, J=5.2 Hz, 1H), 8.10 (d, J=5.2 Hz, 1H)

2-Benzyloxypyridine-4-methanol hydrochloride (Reference compound 9-4)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.52 (s, 2H), 5.36 (s, 2H), 6.89 (m, 1H), 6.98 (m, 1H), 7.32 (d, J=7.0Hz, 1H), 7.37 (t, J=7.0 Hz, 2H), 7.43 (d, J=7.0 Hz, 2H), 8.10 (d, J=5.5Hz, 1H), 7.00-8.20 (br s, 1H)

Reference Example 10 2-Cyano-4-(trimethylsilyloxymethyl)pyridine(Reference compound No. 10-1)

Trimethylsilylnitrile (8.0 mL, 60 mmol) and dimethylcarbamoyl chloride(4.1 mL, 45 mmol) were added to a solution of 4-pyridylcarbinol-N-oxide(5.1 g, 41 mmol) in methylen chloride (200 mL) at room temperature, thenthe mixture was stirred for 4 days. The solvent was evaporated underreduced pressure, then diethyl ether (40 mL) was added to the residue,and the resulting insoluble matter was filtered out. The filtrate wasevaporated under reduced pressure, and then the resulting residue waspurified by silica gel column chromatography to give 5.8 g of the titlereference compound as a pale yellow solid. (Yield 68%)

¹H-NMR (400 MHz, DMSO-d₆)

δ 0.16 (s, 9H), 4.79 (s, 2H), 7.66 (m, 1H), 7.92 (dd, J=1.6, 0.7 Hz,1H), 8.71 (dd, J=5.1, 0.7 Hz, 1H)

Reference Example 11 2-Cyanopyridine-4-methanol (Reference compound No.11-1)

Tetra-n-butylammonium fluoride trihydrate (1.1 g, 3.5 mmol) was added toa solution of 2-cyano-4-(trimethylsilyloxymethyl)pyridine (600 mg, 2.9mmol, Reference compound No. 10-1) in tetrahydrofuran (15 mL) at roomtemperature, then the mixture was stirred for 3 hours. The solvent wasevaporated under reduced pressure, and then the resulting residue waspurified by silica gel column chromatography to give 120 mg of the titlereference compound as a yellow solid. (Yield 32%)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.61 (d, J=5.8 Hz, 2H), 5.64 (t, J=5.8 Hz, 1H), 7.67 (ddd, J=4.0, 1.5,0.6 Hz, 1H), 7.92 (dd, J=1.5, 0.9 Hz, 1H), 8.69 (dd, J=5.0, 0.6 Hz, 1H)

Reference Example 12 2-Ethoxycarbonylpyridine-4-methanol (Referencecompound No. 12-1)

Trimethylsilyl chloride (0.4 mL, 3.0 mmol) was added to a solution of2-cyanopyridine-4-methanol (200 mg, 1.5 mmol, Reference compound No.11-1) in ethanol (3 mL) at 50° C. under a nitrogen atmosphere, then themixture was stirred for 12 hours. The mixture was allowed to stand, anda little water and sodium carbonate (160 mg, 1.5 mmol) were addedthereto. The solution was dried over anhydrous magnesium sulfate, thenthe solvent was evaporated under reduced pressure. The resulting residuewas purified by silica gel column chromatography to give 43 mg of thetitle reference compound as a white solid. (Yield 16%)

¹H-NMR (500 MHz, DMSO-d₆)

δ 1.33 (t, J=7.0 Hz, 3H), 4.35 (q, J=7.0 Hz, 2H), 4.62 (d, J=5.8 Hz,2H), 5.56 (t, J=5.8 Hz, 1H), 7.55 (m, 1H), 8.01 (dd, J=1.6, 0.6 Hz, 1H),8.63 (dd, J=4.6, 0.6 Hz, 1H)

As described below, Reference compound (No. 12-2) was obtained by amethod similar to Reference Example 12.

2-Methoxycarbonylpyridine-4-methanol (Reference compound No. 12-2)

¹H-NMR (500 MHz, DMSO-d₆)

δ 3.88 (s, 3H), 4.62 (d, J=5.8 Hz, 2H), 5.57 (t, J=5.8 Hz, 1H), 7.56(dt, J=4.9, 0.9 Hz, 1H), 8.02 (dd, J=1.5, 0.6 Hz, 1H), 8.64 (dd, J=4.9,0.6 Hz, 1H)

Reference Example 13 2-Carbamoylpyridine-4-methanol (Reference compoundNo. 13-1)

Trimethylsilyl chloride (27 mL) and a suspension of2-cyanopyridine-4-methanol (1.6 g, 11 mmol, Reference compound 11-1) inethanol (20 mL) were added to ethanol (14 mL) at room temperature undera nitrogen atmosphere, and then the mixture was stirred at 50° C. for5.5 hours. The mixture was allowed to stand, and water (27 mL) andsodium carbonate (2.3 g, 22 mmol) were added thereto. The solvent wasevaporated under reduced pressure, ethanol (100 mL) was added thereto,and the resulting insoluble matter was filtered out. The filtrate wasevaporated under reduced pressure, then the resulting residue was driedat 50° C. under reduced pressure to the title reference compoundincluding inorganic salt.

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.61 (d, J=6.1 Hz, 2H), 5.52 (t, J=6.1 Hz, 1H), 7.50 (dt, J=4.9, 0.9Hz, 1H), 7.60 (s, 1H), 8.01 (d, J=0.9 Hz, 1H), 8.08 (s, 1H), 8.55 (d,J=4.9 Hz, 1H)

Reference Example 142-(2-Chloropyridin-4-ylmethylthio)pyridine-3-carboxylic acid (Referencecompound No. 14-1)

Triphenylphosphine (19 g, 71 mmol) and carbon tetrabromide (29 g, 88mmol) were added to a solution of 2-chloropyridine-4-methanol (8.5 g, 59mmol, Reference compound No. 7-1) in methylen chloride (250 mL), thenthe mixture was stirred at room temperature for 1 hour. The solvent wasevaporated under reduced pressure, and then the resulting residue waspurified by silica gel column chromatography to give4-bromomethyl-2-chloropyridine. Immediately, 2-mercaptonicotinic acid(9.1 g, 59 mmol) was added to a solution of this bromo intermediate inN,N-dimethylformamide (100 mL) under ice-cooling, then triethylamine (25mL, 180 mmol) was added dropwise thereto. The reaction mixture wasstirred at room temperature for 15 hours, then diethyl ether (100 mL)and water (600 mL) were added thereto, and the organic layer and theaqueous layer were separated. The aqueous layer was adjusted to pH 6with 2N hydrochloric acid, the precipitated solid was filtered off. Thesolid was washed with water and diethyl ether, and dried at 50° C. underreduced pressure to give 12 g of the title reference compound as ayellow solid. (Yield 73%)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.40 (s, 2H), 7.27 (dd, J=7.7, 4.7 Hz, 1H), 7.45 (dd, J=5.2, 1.5 Hz,1H), 7.55 (d, J=0.6 Hz, 1H), 8.24 (dd, J=7.7, 1.9 Hz, 1H), 8.30 (dd,J=5.2, 0.6 Hz, 1H), 8.64 (dd, J=4.7, 1.9 Hz, 1H), 13.52 (s, 1H)

As described below, Reference compounds (No. 14-2˜10) were obtained by amethod similar to Reference Example 14.

2-(2-Methylthiopyridin-4-ylmethylthio)pyridine-3-carboxylic acid(Reference compound No. 14-2)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.47 (s, 3H), 4.32 (s, 2H), 7.13 (dd, J=5.1, 1.4 Hz, 1H), 7.27 (dd,J=7.7, 4.8 Hz, 1H), 7.32 (s, 1H), 8.22 (dd, J=7.7, 1.8 Hz, 1H), 8.31(dd, J=5.1, 0.7 Hz, 1H), 8.63 (dd, J=4.8, 1.8 Hz, 1H), 13.50 (s, 1H)

2-(2-Methoxypyridin-4-ylmethylthio)pyridine-3-carboxylic acid (Referencecompound No. 14-3)

¹H-NMR (400 MHz, DMSO-d₆)

δ 3.80 (s, 3H), 4.33 (s, 2H), 6.82 (s, 1H), 7.00 (dd, J=5.1, 1.4 Hz,1H), 7.26 (dd, J=8.1, 4.7 Hz, 1H), 8.05 (d, J=5.1 Hz, 1H), 8.21 (dd,J=8.1, 1.8 Hz, 1H), 8.63 (dd, J=4.7, 1.8 Hz, 1H), 13.48 (s, 1H)

2-(2-Ethoxypyridin-4-ylmethylthio)pyridine-3-carbooxylic acid (Referencecompound No. 14-4)

¹H-NMR (500 MHz, DMSO-d₆)

δ 1.28 (t, J=7.0 Hz, 3H), 4.22-4.30 (m, 2H), 4.33 (s, 2H), 6.79 (s, 1H),6.98 (dd, J=5.3, 1.4 Hz, 1H), 7.27 (dd, J=7.7, 4.7 Hz, 1H), 8.03 (d,J=5.3 Hz, 1H), 8.23 (dd, J=7.7, 1.8 Hz, 1H), 8.64 (dd, J=4.7, 1.8 Hz,1H), 13.50 (br s, 1H)

2-(2-Isopropoxypyridin-4-ylmethylthio)pyridine-3-carboxylic acid(Reference compound No. 14-5)

¹H-NMR (500 MHz, DMSO-d₆)

δ 1.25 (d, J=6.1 Hz, 6H), 4.30 (s, 2H), 5.21 (m, 1H), 6.72 (s, 1H), 6.95(d, J=5.3 Hz, 1H), 7.25 (dd, J=7.6, 4.6 Hz, 1H), 8.02 (d, J=5.3 Hz, 1H),8.21 (d, J=7.6 Hz, 1H), 8.61 (m, 1H), 13.50 (br s, 1H)

2-(2-Cyanopyridin-4-ylmethylthio)pyridine-3-carboxylic acid (Referencecompound No. 14-6)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.44 (s, 2H), 7.28 (dd, J=7.9, 4.7 Hz, 1H), 7.78 (dd, J=5.2, 1.8 Hz,1H), 8.08 (s, 1H), 8.24 (dd, J=7.9, 1.8 Hz, 1H), 8.63-8.64 (m, 2H),13.55 (s, 1H)

2-(2-Ethoxycarbonylpyridin-4-ylmethylthio)pyridine-3-carboxylic acid(Reference compound No. 14-7)

¹H-NMR (400 MHz, DMSO-d₆)

δ 1.32 (t, J=7.1 Hz, 3H), 4.33 (q, J=7.1 Hz, 2H), 4.47 (s, 2H), 7.27(dd, J=7.6, 4.6 Hz, 1H), 7.67 (dd, J=4.9, 1.7 Hz, 1H), 8.10 (m, 1H),8.23 (dd, J=7.6, 2.0 Hz, 1H), 8.59 (dd, J=4.9, 0.7 Hz, 1H), 8.62 (dd,J=4.6, 2.0 Hz, 1H), 13.53 (s, 1H)

3-(2-Chloropyridin-4-ylmethylthio)thiophene-2-carboxylic acid (Referencecompound No. 14-8)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.38 (s, 2H), 7.19 (d, J=5.2 Hz, 1H), 7.49 (dd, J=5.2, 1.5 Hz, 1H),7.59 (d, J=0.9 Hz, 1H), 7.86 (d, J=5.2 Hz, 1H), 8.36 (dd, J=5.2, 0.9 Hz,1H), 13.11 (s, 1H)

2-(2-Methoxycarbonylpyridin-4-ylmethylthio)pyridine-3-carboxylic acid(Reference compound No. 14-9)

¹H-NMR (400 MHz, DMSO-d₆)

δ 3.86 (s, 3H), 4.46 (s, 2H), 7.26 (dd, J=7.7, 4.8 Hz, 1H), 7.67 (dd,J=4.8, 1.4 Hz, 1H), 8.10 (d, J=1.4 Hz, 1H), 8.22 (dd, J=7.7, 1.8 Hz,1H), 8.58 (d, J=4.8 Hz, 1H), 8.61 (dd, J=4.8, 1.8 Hz, 1H), 13.52 (br s,1H)

2-(2-Methylpyridin-4-ylmethylthio)pyridine-3-carboxylic acid (Referencecompound No. 14-10)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.65 (s, 3H), 4.53 (s, 2H), 7.28 (dd, J=7.7, 4.8 Hz, 1H), 7.84-7.90(m, 2H), 8.24 (dd, J=7.7, 1.8 Hz, 1H), 8.59-8.62 (m, 2H), 13.50-13.65(br s, 1H)

Reference Example 15 3-Iodopyrazine-2-carboxylic acid methyl ester(Reference compound No. 15-1)

Isoamyl nitrite (5.2 mL, 39 mmol) was added to a suspension of3-aminopyrazine-2-carboxylic acid methyl ester (1.9 g, 12 mmol) indiiodomethane (20 mL) at 85° C., then the mixture was stirred at 100° C.for 15 hours. The reaction mixture was allowed to stand and purified bysilica gel column chromatography to give 1.4 g of the title referencecompound as a pale yellow solid. (Yield 44%)

¹H-NMR (500 MHz, CDCl₃)

δ 4.04 (s, 3H), 8.47 (d, J=2.1 Hz, 1H), 8.56 (d, J=2.1 Hz, 1H)

As described below, Reference compounds (No. 15-2-4) were obtained by amethod similar to Reference Example 15.

5-Iodo-1-methylpyrazole-4-carboxylic acid ethyl ester (Referencecompound No. 15-2)

¹H-NMR (400 MHz, DMSO-d₆)

δ 1.28 (t, J=7.1 Hz, 3H), 3.92 (s, 3H), 4.23 (q, J=7.1 Hz, 2H), 7.92 (s,1H)

2-Iodothiophene-3-carboxylic acid methyl ester (Reference compound No.15-3)

¹H-NMR (500 MHz, CDCl₃)

δ 3.89 (s, 3H), 7.32 (d, J=5.7 Hz, 1H), 7.41 (d, J=5.7 Hz, 1H)

4-Iodothiophene-3-carboxylic acid methyl ester (Reference compound No.15-4)

¹H-NMR (400 MHz, CDCl₃)

δ 3.89 (s, 3H), 7.51 (d, J=3.5 Hz, 1H), 8.07 (d, J=3.5 Hz, 1H)

Reference Example 16 3-(4-Pyridylmethylthio)pyrazine-2-carboxylic acidmethyl ester (Reference compound No. 16-1)

3-Iodopyrazine-2-carboxylic acid methyl ester (0.37 g, 1.4 mmol,Reference compound No. 15-1), 4-pyridinemethanethiol hydrochloride (0.24g, 1.5 mmol) and potassium carbonate (0.41 g, 3.0 mmol) were suspendedin N,N-dimethylformamide (10 mL), then the mixture was stirred at 60° C.for 1 hour. The reaction mixture was diluted with ethyl acetate (70 mL),and washed with water (100 mL) twice and brine (70 mL) twice. The ethylacetate layer was dried over anhydrous magnesium sulfate, and then thesolvent was evaporated under reduced pressure. The resulting residue wasfiltered off with diisopropyl ether to give 0.25 g of the titlereference compound as a pale cinnabar solid. (Yield 69%)

¹H-NMR (500 MHz, CDCl₃)

δ 4.03 (s, 3H), 4.37 (s, 2H), 7.35 (dd, J=4.3, 1.5 Hz, 2H), 8.39 (d,J=2.1 Hz, 1H), 8.52 (dd, J=4.3, 1.5 Hz, 2H), 8.53 (d, J=2.1 Hz, 1H)

As described below, Reference compounds (No. 16-2˜5) were obtained by amethod similar to Reference Example 16.

1-Methyl-5-(4-pyridylmethylthio)pyrazole-4-carboxylic acid ethyl ester(Reference compound No. 16-2)

¹H-NMR (400 MHz, CDCl3)

δ 1.40 (t, J=7.1 Hz, 3H), 3.56 (s, 3H), 4.11 (s, 2H), 4.36 (q, J=7.1 Hz,2H), 6.99 (dd, J=4.6, 1.5 Hz, 2H), 7.95 (s, 1H), 8.48 (dd, J=4.6, 1.5Hz, 2H)

2-(4-Pyridylmethylthio)thiophene-3-carboxylic acid methyl ester(Reference compound No. 16-3)

¹H-NMR (400 MHz, CDCl₃)

δ 3.87 (s, 3H), 4.20 (s, 2H), 7.09 (d, J=5.5 Hz, 1H), 7.30 (dd, J=4.4,1.5 Hz, 2H), 7.41 (d, J=5.5 Hz, 1H), 8.55 (dd, J=4.4, 1.5 Hz, 2H)

4-(4-Pyridylmethylthio)thiophene-3-carboxylic acid methyl ester(Reference compound No. 16-4)

¹H-NMR (400 MHz, CDCl₃)

δ 3.88 (s, 3H), 4.10 (s, 2H), 6.77 (d, J=3.3 Hz, 1H), 7.33-7.35 (m, 2H),8.16 (d, J=3.3 Hz, 1H), 8.67 (br s, 2H)

3-(4-Pyridylmethylthio)thiophene-2-carboxylic acid methyl ester(Reference compound No. 16-5)

¹H-NMR (500 MHz, DMSO-d₆)

δ 3.85 (s, 3H), 4.75 (s, 2H), 7.17 (d, J=5.3 Hz, 1H), 7.45 (dd, J=4.3,1.5 Hz, 2H), 7.88 (d, J=5.3 Hz, 1H), 8.50 (dd, J=4.3, 1.5 Hz, 2H)

Reference Example 17 3-(4-Pyridylmethylthio)pyrazine-2-carboxylic acid(Reference compound No. 17-1)

3-(4-Pyridylmethylthio)pyrazine-2-carboxylic acid methyl ester (0.21 g,0.80 mmol, Reference compound No. 16-1) was dissolved in methanol (4.0mL), a 1 N aqueous sodium hydroxide solution (4.0 mL) was added thereto,and then the mixture was stirred at room temperature for 7 hours. Thesolvent was evaporated under reduced pressure, water was added to theresulting residue, and then the mixture was adjusted to approximately pH5 with 1N hydrochloric acid under ice-cooling. The precipitated solidwas filtered off to give 0.17 g of the title reference compound as a redsolid. (Yield 85%)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.38 (s, 2H), 7.43 (dd, J=4.6, 1.5 Hz, 2H), 8.47 (d, J=2.4 Hz, 1H),8.48 (dd, J=4.6, 1.5 Hz, 2H), 8.70 (d, J=2.4 Hz, 1H), 13.74 (br s, 1H)

As described below, Reference compounds (No. 17-2-4) were obtained by amethod similar to Reference Example 17.

1-Methyl-5-(4-pyridylmethylthio)pyrazole-4-carboxylic acid (Referencecompound No. 17-2)

¹H-NMR (500 MHz, DMSO-d₆)

δ 3.48 (s, 3H), 4.27 (s, 2H), 7.07 (d, J=4.6, 1.5 Hz, 2H), 7.73 (s, 1H),8.40 (dd, J=4.6, 1.5 Hz, 2H)

2-(4-Pyridylmethylthio)thiophene-3-carboxylic acid (Reference compoundNo. 17-3)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.32 (s, 2H), 7.31 (d, J=5.4 Hz, 1H), 7.41 (d, J=5.4 Hz, 1H), 7.43(dd, J=4.4, 1.7 Hz, 2H), 8.52 (dd, J=4.4, 1.7 Hz, 2H), 12.83 (s, 1H)

4-(4-Pyridylmethylthio)thiophene-3-carboxylic acid (Reference compoundNo. 17-4)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.20 (s, 2H), 7.20 (m, 1H), 7.44-7.45 (m, 2H), 8.36 (m, 1H), 8.50-8.51(m, 2H), 12.86 (s, 1H)

Reference Example 18 N-(3,5-Dimethylphenyl)-2-thiopyridone-3-carboxamide(Reference compound No. 18-1)

Pyridine (30 mL, 0.37 mol) and thionyl chloride (20 mL, 0.23 mol) wereadded to a solution of 2-mercaptonicotinic acid (10 g, 64 mmol) inmethylene chloride (80 mL) under ice-cooling, then the mixture wasstirred for 1 hour. The reaction mixture was concentrated under reducedpressure, then the resulting residue was suspended in chloroform (80 mL)and pyridine (20 mL, 0.26 mmol). 3,5-Xylidine (8.0 mL, 64 mmol) wasadded to the suspension, and the mixture was stirred at room temperaturefor 4 hours. The reaction mixture was concentrated under reducedpressure, ethyl acetate and ethanol were added to the precipitatedsolid, then the solid was filtered off. The solid was dried underreduced pressure to give 1.9 g of the title reference compound as a pinksolid. (Yield 11%)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.27 (s, 6H), 6.77 (d, J=0.6 Hz, 1H), 7.10 (dd, J=7.6, 6.0 Hz, 1H),7.34 (s, 2H), 8.03 (dd, J=6.0, 1.8 Hz, 1H), 8.55 (dd, J=7.6, 1.8 Hz,1H), 12.90 (s, 1H), 14.18 (s, 1H)

Example 1N-(4-Chlorophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-1)

N,N-Diisopropylethylamine (1.6 mL, 8.9 mmol) ando-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (1.6 g, 4.3 mmol) were added to a solution of2-(4-pyridylmethylthio)pyridine-3-carboxylic acid (1.0 g, 4.1 mmol,Reference compound No. 1-1) and 4-chloroaniline (0.54 g, 4.3 mmol) inN,N-dimethylformamide (20 mL), then the mixture was stirred for 3 hours.A saturated aqueous sodium hydrogencarbonate solution (150 mL) was addedto the reaction mixture, then the whole was extracted with ethyl acetate(150 mL). The ethyl acetate layer was washed with a saturated aqueoussodium hydrogencarbonate solution (150 mL) twice and saturated brine(150 mL) twice, and was dried over anhydrous magnesium sulfate. Thesolvent was evaporated under reduced pressure. The precipitated solidwas filtered off, was washed with diethyl ether:ethyl acetate (10:1),and was dried under reduced pressure to give 1.3 g of the targetcompound as a white solid. (Yield 91%)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.42 (s, 2H), 7.30 (dd, J=7.6, 4.7 Hz, 1H), 7.37-7.43 (m, 4H), 7.72(d, J=7.6 Hz, 2H), 7.98 (dd, J=7.6, 1.7 Hz, 1H), 8.45 (dd, J=4.5, 1.8Hz, 2H), 8.59 (dd, J=4.7, 1.7, 1H), 10.60 (s, 1H)

¹³C-NMR (100 MHz, DMSO-d₆)

δc 32.0, 119.3, 121.3, 124.0, 127.5, 128.5, 129.8, 135.8, 137.6, 147.7,149.3, 150.2, 155.9, 164.6

Below compounds (No. 1-2˜308) were obtained by a method similar toExample 1.

N-(2,2-Dimethylpropyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-2)

¹H-NMR (400 MHz, CDCl₃)

δ 1.00 (s, 9H), 3.27 (d, J=6.4 Hz, 2H), 4.44 (s, 2H), 6.23 (br s, 1H),7.10 (dd, J=7.6, 4.4 Hz, 1H), 7.34 (dd, J=4.4, 1.6 Hz, 2H), 7.81 (dd,J=7.6, 1.8 Hz, 1H), 8.48-8.51 (m, 3H)

N-Cyclohexyl-2-(4-pyridylmethylthio)pyridine-3-carboxamide (Compound No.1-3)

¹H-NMR (400 MHz, DMSO-d₆)

δ 1.00-1.35 (m, 5H), 1.50-1.85 (m, 5H), 3.67 (m, 1H) 4.37 (s, 2H), 7.20(dd, J=7.6, 4.9 Hz, 1H), 7.39 (dd, J=4.4, 1.7 Hz, 2H), 7.76 (dd, J=7.6,1.7 Hz, 1H), 8.35 (d, J=7.8 Hz, 1H), 8.45 (dd, J=4.4, 1.7 Hz, 2H), 8.50(dd, J=4.9, 1.7 Hz, 1H)

3-Morpholinocarbonyl-2-(4-pyridylmethylthio)pyridine (Compound No. 1-4)

¹H-NMR (400 MHz, DMSO-d₆)

δ 3.06 (br s, 2H), 3.47 (br s, 2H), 3.62 (br s, 4H), 4.47 (s, 2H), 7.25(dd, J=7.6, 4.9 Hz, 1H), 7.37 (dd, J=4.4, 1.7 Hz, 2H), 7.65 (dd, J=7.6,1.9 Hz, 1H), 8.46 (dd, J=4.4, 17 Hz, 2H), 8.53 (dd, J=4.9, 1.9 Hz, 1H)

N′-(4-Chlorophenyl)-2-(4-pyridylmethylthio)pyridine-3-carbohydrazide(Compound No. 1-5)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.40 (s, 2H), 6.82 (d, J=8.9 Hz, 2H), 7.19 (d, J=8.9 Hz, 2H), 7.28(dd, J=7.6, 4.9 Hz, 1H), 7.40 (dd, J=4.6, 1.5 Hz, 2H), 7.98 (dd, J=7.6,1.8 Hz, 1H), 8.19 (d, J=2.5 Hz, 1H), 8.47 (dd, J=4.6, 1.5 Hz, 2H), 8.59(dd, J=4.5, 1.8 Hz, 1H), 10.37 (s, 1H)

N′-tert-Butyl-2-(4-pyridylmethylthio)pyridine-3-carbohydrazide (CompoundNo. 1-6)

¹H-NMR (500 MHz, DMSO-d₆)

δ 1.07 (s, 9H), 4.40 (s, 2H), 4.92 (br s, 1H), 7.22 (dd, J=7.5, 4.8 Hz,1H), 7.39 (dd, J=4.4, 1.6 Hz, 2H), 7.78 (dd, J=7.5, 1.8 Hz, 1H), 8.45(dd, J=4.4, 1.6 Hz, 2H), 8.53 (dd, J=4.8, 1.8 Hz, 1H), 9.85 (s, 1H)

N-(4-Chlorobenzyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-7)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.37 (s, 2H), 4.42 (d, J=5.8 Hz, 2H), 7.23 (dd, J=7.6, 4.4 Hz, 1H),7.36 (dd, J=4.4, 1.9 Hz, 2H), 7.37-7.42 (m, 4H), 7.88 (dd, J=7.6, 1.7Hz, 1H), 8.45 (dd, J=4.5, 1.7 Hz, 2H), 8.55 (dd, J=4.4, 1.7 Hz, 1H),9.10 (t, J=5.8 Hz, 1H)

N-[2-(4-Chlorophenyl)ethyl]-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-8)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.82 (t, J=7.0 Hz, 2H), 3.43 (td, J=7.0, 5.8 Hz, 2H), 4.36 (s, 2H),7.20 (dd, J=7.6, 4.6 Hz, 1H), 7.27 (d, J=8.6 Hz, 2H), 7.32 (d, J=8.6 Hz,2H), 7.38 (dd, J=4.3, 1.5 Hz, 2H), 7.71 (dd, J=7.6, 1.5 Hz, 1H), 8.45(dd, J=4.3, 1.5 Hz, 2H), 8.52 (dd, J=4.6, 1.5 Hz, 1H), 8.59 (t, J=5.8Hz, 1H)

N-[2-(4-Methoxyphenyl)ethyl]-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-9)

1H-NMR (400 MHz, DMSO-d₆)

δ 2.75 (t, J=7.2 Hz, 2H), 3.39 (td, J=7.2, 5.5 Hz, 2H), 3.71 (s, 3H),4.37 (s, 2H), 6.84 (dd, J=6.5, 2.2 Hz, 2H), 7.15 (d, J=8.6 Hz, 2H), 7.21(dd, J=7.5, 4.8 Hz, 1H), 7.39 (dd, J=4.4, 1.6 Hz, 2H), 7.74 (dd, J=7.5,1.8 Hz, 1H), 8.45 (dd, J=4.4, 1.6 Hz, 2H), 8.52 (dd, J=4.8, 1.8 Hz, 1H),8.59 (t, J=5.5 Hz, 1H)

O-Benzyl-2-(4-pyridylmethylthio)pyridine-3-carbohydroxamate (CompoundNo. 1-10)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.40 (s, 2H), 4.93 (s, 2H), 7.21 (dd, J=7.6, 4.9 Hz, 1H), 7.30-7.50(m, 7H), 7.70 (d, J=6.4 Hz, 1H), 8.46 (d, J=4.6 Hz, 2H), 8.55 (dd,J=4.9, 1.5 Hz, 1H), 11.73 (s, 1H)

N-(1H-Benzimidazol-2-yl)methyl-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-11)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.36 (s, 2H), 4.66 (d, J=5.8 Hz, 2H), 7.12-7.16 (m, 2H), 7.27 (dd,J=7.6, 4.9 Hz, 1H), 7.39 (dd, J=4.3, 1.5 Hz, 2H), 7.49-7.54 (m, 2H),8.06 (dd, J=7.6, 1.8 Hz, 1H), 8.45 (dd, J=4.3, 1.5 Hz, 2H), 8.57 (dd,J=4.9, 1.8 Hz, 1H), 9.24 (t, J=5.8 Hz, 1H), 12.40 (br s, 1H)

N-[2-(Indol-3-yl)ethyl]-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-12)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.89-2.98 (m, 2H), 3.46-3.55 (m, 2H), 4.37 (s, 2H), 6.97 (m, 1H), 7.07(m, 1H), 7.18-7.24 (m, 2H), 7.34 (d, J=8.1 Hz, 1H), 7.39 (dd, J=4.4, 1.7Hz, 2H), 7.56 (d, J=7.8 Hz, 1H), 7.76 (m, 1H), 8.45 (dd, J=4.4, 1.7 Hz,2H), 8.52 (dd, J=4.6, 1.7 Hz, 1H), 8.66 (t, J=5.6 Hz, 1H), 10.83 (br s,1H)

N-(2-Phenoxyethyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-13)

¹H-NMR (500 MHz, DMSO-d₆)

δ3.59 (td, J=5.8, 5.5 Hz, 2H), 4.09 (t, J=5.8 Hz, 2H), 4.36 (s, 2H),6.90-7.00 (m, 3H), 7.22 (dd, J=7.6, 4.6 Hz, 1H), 7.25-7.32 (m, 2H), 7.37(dd, J=4.6, 1.5 Hz, 2H), 7.82 (dd, J=7.6, 1.8 Hz, 1H), 8.44 (dd, J=4.6,1.5 Hz, 2H), 8.53 (m, 1H), 8.78 (dd, J=4.6, 1.8 Hz, 1H)

N-(4-Chlorophenyl)-N-methyl-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-14)

¹H-NMR (500 MHz, DMSO-d₆)

δ3.30 (br s, 3H), 4.42 (s, 2H), 7.03 (br s, 1H), 7.08-7.25 (m, 4H), 7.32(d, J=4.5 Hz, 2H), 7.50 (br s, 1H), 8.36 (br s, 1H), 8.47 (d, J=4.5 Hz,2H)

N-(4-Chlorophenyl)-N-ethyl-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-15)

¹H-NMR (400 MHz, CDCl₃)

δ 1.15-1.28 (m, 3H), 3.80-4.00 (m, 2H), 4.41 (s, 2H), 6.82 (m, 1H),6.88-7.20 (m, 5H), 7.28 (d, J=4.5 Hz, 2H), 8.29 (br s, 1H), 8.51 (d,J=4.5 Hz, 2H)

N-(5-Methylpyridin-2-yl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-16)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.28 (s, 3H), 4.41 (s, 2H), 7.25 (dd, J=7.5, 4.9 Hz, 1H), 7.40 (dd,J=4.4, 1.7 Hz, 2H), 7.66 (dd, J=8.8, 2.2 Hz, 1H), 7.98 (dd, J=7.5, 1.7Hz, 1H), 8.03 (d, J=8.8 Hz, 1H), 8.20 (d, J=2.2 Hz, 1H), 8.45 (dd,J=4.4, 1.7 Hz, 2H), 8.57 (dd, J=4.9, 1.7 Hz, 1H), 10.94 (s, 1H)

N-(3-Pyridyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide (CompoundNo. 1-17)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.32 (dd, J=7.6, 4.9 Hz, 1H), 7.40 (dd, J=4.9, 1.5 Hz,2H), 8.03 (dd, J=7.6, 1.8 Hz, 1H), 8.13 (d, J=8.3 Hz, 1H), 8.33 (dd,J=4.9, 1.5 Hz, 1H), 8.46 (dd, J=4.9, 1.5 Hz, 2H), 8.60 (m, 1H), 8.64 (d,J=2.4 Hz, 1H), 8.84 (d, J=4.9, 1.5 Hz, 1H), 10.69 (s, 1H)

N-(2-Chloropyridin-5-yl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-18)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.42 (s, 2H), 7.32 (dd, J=7.6, 4.9 Hz, 1H), 7.40 (dd, J=4.3, 1.5 Hz,2H), 7.54 (d, J=8.9 Hz, 1H), 8.04 (dd, J=7.6, 1.8 Hz, 1H), 8.17 (dd,J=8.9, 2.7 Hz, 1H), 8.45 (dd, J=4.3, 1.5 Hz, 2H), 8.61 (dd, J=4.9, 1.8Hz, 1H), 8.70 (d, J=2.7 Hz, 1H), 10.83 (s, 1H)

N-(4-Pyridyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide (CompoundNo. 1-19)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.32 (dd, J=7.6, 4.8 Hz, 1H), 7.40 (dd, J=4.5, 1.7 Hz,2H), 7.67 (dd, J=4.6, 1.6 Hz, 2H), 8.02 (dd, J=7.6, 1.8 Hz, 1H), 8.45(dd, J=4.5, 1.7 Hz, 2H), 8.48 (dd, J=4.6, 1.6 Hz, 2H), 8.61 (dd, J=4.8,1.8 Hz, 1H), 10.84 (s, 1H)

2-(4-Pyridylmethylthio)-N-(3-quinolyl)pyridine-3-carboxamide (CompoundNo. 1-20)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.44 (s, 2H), 7.34 (dd, J=7.6, 4.8 Hz, 1H), 7.42 (dd, J=4.5, 1.6 Hz,2H), 7.60 (m, 1H), 7.68 (m, 1H), 7.98 (d, J=8.6 Hz, 2H), 8.11 (dd,J=7.6, 1.5 Hz, 1H), 8.46 (dd, J=4.5, 1.6 Hz, 2H), 8.64 (dd, J=4.8, 1.8Hz, 1H), 8.83 (d, J=2.1 Hz, 1H), 9.02 (d, J=2.5 Hz, 1H), 10.96 (s, 1H)

2-(4-Pyridylmethylthio)-N-(6-quinolyl)pyridine-3-carboxamide (CompoundNo. 1-21)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.33 (dd, J=7.6, 4.7 Hz, 1H), 7.40-7.45 (m, 2H), 7.51(dd, J=8.3, 4.4 Hz, 1H), 7.89 (dd, J=9.0, 2.2 Hz, 1H), 8.00-8.10 (m,2H), 8.35 (d, J=8.0 Hz, 1H), 8.45-8.50 (m, 2H), 8.53 (m, 1H), 8.62 (dd,J=4.9, 1.7 Hz, 1H), 8.82 (dd, J=4.2, 1.7 Hz, 1H), 10.82 (s, 1H)

N-(3-Isoquinolyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-22)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.28 (dd, J=7.6, 4.9 Hz, 1H), 7.40 (d, J=6.1 Hz, 2H),7.58 (t, J=7.3 Hz, 1H), 7.75 (dt, J=7.3, 0.9 Hz, 1H), 7.97 (d, J=7.9 Hz,1H), 8.05 (dd, J=7.6, 1.8 Hz, 1H), 8.09 (d, J=8.2 Hz, 1H), 8.45 (dd,J=4.6, 1.5 Hz, 2H), 8.59 (dd, J=4.6, 1.8 Hz, 2H), 9.19 (s, 1H), 11.20(s, 1H)

N-(Indazol-5-yl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide (CompoundNo. 1-23)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.42 (s, 2H), 7.30 (dd, J=7.6, 4.9 Hz, 1H), 7.41 (dd, J=4.6, 1.5 Hz,2H), 7.50-7.60 (m, 2H), 7.99 (dd, J=7.6, 1.5 Hz, 1H), 8.07 (s, 1H), 8.23(s, 1H), 8.46 (dd, J=4.6, 1.5 Hz, 2H), 8.59 (dd, J=4.9, 1.5 Hz, 1H),10.48 (br, 1H), 13.04 (br s, 1H)

N-(1-Naphthyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide (CompoundNo. 1-24)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.45 (s, 2H), 7.36 (m, 1H), 7.43 (d, J=5.8 Hz, 2H), 7.50-7.60 (m, 3H),7.70 (m, 1H), 7.85 (d, J=8.2 Hz, 1H), 7.98 (m, 1H), 8.05-8.20 (m, 2H),8.45-8.50 (m, 2H), 8.62 (d, J=3.7 Hz, 1H), 10.57 (s, 1H)

N-(5-Methylisoxazol-3-yl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-25)

¹H-NMR (500 MHz, CDCl₃)

δ 2.43 (s, 3H), 4.43 (s, 2H), 6.85 (s, 1H), 7.16 (dd, J=7.6, 4.9 Hz,1H), 7.34 (dd, J=4.6, 1.5 Hz, 2H), 7.95 (dd, J=7.6, 1.7 Hz, 1H), 8.46(dd, J=4.6, 1.5 Hz, 2H), 8.57 (dd, J=4.9, 1.7 Hz, 1H), 9.25 (br s, 1H)

2-(4-Pyridylmethylthio)-N-(2-thiazolyl)pyridine-3-carboxamide (CompoundNo. 1-26)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.42 (s, 2H), 7.26-8.02 (m, 2H), 7.43 (d, J=5.8 Hz, 2H), 7.56 (d,J=3.4 Hz, 1H), 8.15 (d, J=7.3 Hz, 1H), 8.47 (d, J=5.8 Hz, 2H), 8.61 (dd,J=4.7, 1.4 Hz, 1H), 12.78 (s, 1H)

N-(6-Chlorobenzothiazol-2-yl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-27)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.44 (s, 2H), 7.33 (dd, J=7.6, 4.8 Hz, 1H), 7.42 (dd, J=4.5, 1.5 Hz,2H), 7.48 (dd, J=8.6, 2.1 Hz, 1H), 7.77 (d, J=8.6 Hz, 1H), 8.17 (d,J=2.1 Hz, 1H), 8.23 (dd, J=7.6, 1.5 Hz, 1H), 8.46 (dd, J=4.5, 1.5 Hz,2H), 8.64 (dd, J=4.8, 1.5 Hz, 1H)

N-(4-Chlorophenyl)-2-(2,6-dichloropyridin-4-ylmethylthio)pyridine-3-carboxamide(Compound No. 1-28)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.33 (dd, J=7.6, 4.9 Hz, 1H), 7.43 (d, J=9.0 Hz, 2H),7.60 (s, 2H), 7.73 (d, J=9.0 Hz, 2H), 8.02 (dd, J=7.6, 1.7 Hz, 1H), 8.61(dd, J=4.9, 1.7 Hz, 1H), 10.60 (s, 1H)

N-(3-Chlorophenyl)-2-(2,6-dichloropyridin-4-ylmethylthio)pyridine-3-carboxamide(Compound No. 1-29)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.19 (ddd, J=8.0, 2.0, 0.9 Hz, 1H), 7.34 (dd, J=7.6, 4.9Hz, 1H), 7.40 (t, J=8.1 Hz, 1H), 7.58-7.63 (m, 3H), 7.89 (s, 1H), 8.03(dd, J=7.6, 1.7 Hz, 1H), 8.61 (dd, J=4.9 Hz, 1.7 Hz, 1H), 10.70 (s, 1H)

N-Phenyl-2-(4-pyridylmethylthio)pyridine-3-carboxamide (Compound No.1-30)

¹H-NMR (500 MHz, CDCl₃)

δ 4.45 (s, 2H), 7.13 (dd, J=7.6, 4.6 Hz, 1H), 7.18 (m, 1H), 7.33 (dd,J=4.6, 1.2 Hz, 2H), 7.37 (t, J=7.6 Hz, 2H), 7.61 (d, J=7.6 Hz, 2H), 7.90(d, J=7.6 Hz, 1H), 8.02 (br s, 1H), 8.47 (dd, J=4.6, 1.2 Hz, 2H), 8.53(dd, J=4.6, 1.5 Hz, 1H)

N-(2-Chlorophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-31)

¹H-NMR (400 MHz, CDCl₃)

δ 4.46 (s, 2H), 7.11 (td, J=7.7, 1.5 Hz, 1H), 7.17 (dd, J=7.6, 4.8 Hz,1H), 7.32 (dd, J=7.6, 1.6 Hz, 1H), 7.35 (dd, J=5.9, 1.5 Hz, 2H), 7.41(dd, J=7.7, 1.5 Hz, 1H), 7.93 (dd, J=7.7, 1.5 Hz, 1H), 8.40 (s, 1H),8.48-8.60 (m, 4H)

N-(2-Hydroxymethylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-32)

¹H-NMR (500 MHz, CDCl₃)

δ 4.42 (s, 2H), 4.78 (s, 2H), 6.73 (m, 1H), 7.05-7.16 (m, 2H), 7.19 (m,1H), 7.36 (dd, J=4.6, 1.5 Hz, 2H), 7.37 (m, 1H), 7.88 (dd, J=7.6, 1.7Hz, 1H), 8.27 (m 1H), 8.43 (dd, J=4.6, 1.5 Hz, 2H), 8.52 (dd, J=4.9, 1.7Hz, 1H), 9.49 (s, 1H)

N-(2-Methoxyphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-33)

¹H-NMR (500 MHz, CDCl₃)

δ 3.87 (s, 3H), 4.45 (s, 2H), 6.92 (dd, J=7.9, 1.2 Hz, 1H), 7.02 (td,J=7.6, 0.9 Hz, 1H), 7.10 (dd, J=7.9, 1.2 Hz, 1H), 7.14 (dd, J=7.6, 4.9Hz, 1H), 7.40 (d, J=5.8 Hz, 2H), 7.42 (d, J=6.1 Hz, 1H), 7.88 (dd,J=7.6, 1.5 Hz, 1H), 8.41-8.55 (m, 4H)

N-(2-Ethoxyphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-34)

¹H-NMR (500 MHz, CDCl₃)

δ 1.39 (t, J=7.0 Hz, 3H), 4.11 (q, J=7.0 Hz, 2H), 4.46 (s, 2H), 6.90(dd, J=7.9, 1.2 Hz, 1H), 7.00 (td, J=7.6, 1.2 Hz, 1H), 7.07 (dd, J=7.9,1.5 Hz, 1H), 7.15 (dd, J=7.6, 4.9 Hz, 1H), 7.38 (dd, J=4.6, 1.8 Hz, 2H),7.91 (dd, J=7.6, 1.5 Hz, 1H), 8.51 (m, 2H), 8.53 (dd, J=4.6, 1.8 Hz,2H), 8.56 (m, 1H)

N-(3-Isopropylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-35)

¹H-NMR (400 MHz, DMSO-d₆)

δ 1.20 (d, J=6.8 Hz, 6H), 2.85 (m, 1H), 4.41 (s, 2H), 7.00 (d, J=7.8 Hz,1H), 7.20-7.30 (m, 2H), 7.40 (dd, J=4.4, 1.5 Hz, 2H), 7.51 (d, J=8.1 Hz,1H), 7.80 (s, 1H), 7.96 (dd, J=7.6, 1.5 Hz, 1H), 8.45 (dd, J=4.4, 1.5Hz, 2H), 8.58 (dd, J=4.6, 1.5 Hz, 1H), 10.41 (s, 1H)

N-(3-Methoxyphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-36)

¹H-NMR (500 MHz, CDCl₃)

δ 3.83 (s, 3H), 4.46 (s, 2H), 6.74 (m, 1H), 7.05 (m, 1H), 7.14 (dd,J=7.6, 4.9 Hz, 1H), 7.26 (m, 1H), 7.37 (dd, J=4.6, 1.5 Hz, 2H), 7.39 (m,1H), 7.88-8.03 (m, 2H), 8.50 (dd, J=4.6, 1.5 Hz, 2H), 8.53 (dd, J=4.6,1.8 Hz, 1H)

N-(3-Fluorophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-37)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.42 (s, 2H), 6.95 (m, 1H), 7.30 (dd, J=7.6, 4.9 Hz, 1H), 7.35-7.50(m, 4H), 7.65 (m, 1H), 7.98 (dd, J=7.8, 1.7 Hz, 1H), 8.43-8.50 (m, 2H),8.60 (dd, J=4.9, 1.7 Hz, 1H), 10.68 (s, 1H)

N-(3-Chlorophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-38)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.42 (s, 2H), 7.19 (dd, J=7.9, 1.7 Hz, 1H), 7.29 (dd, J=7.3, 4.8 Hz,1H), 7.37-7.43 (m, 3H), 7.58 (d, J=9.1 Hz, 1H), 7.89 (d, J=1.7 Hz, 1H),7.99 (dd, J=7.3, 1.7 Hz, 1H), 8.45 (dd, J=4.5, 1.5 Hz, 2H), 8.60 (dd,J=4.8, 1.7 Hz, 1H), 10.65 (s, 1H)

N-(3-Bromophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-39)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.42 (s, 2H), 7.28-7.35 (m, 2H), 7.40 (dd, J=4.6, 1.5 Hz, 2H), 7.63(m, 1H), 7.99 (dd, J=7.6, 1.5 Hz, 1H), 8.03 (s, 1H), 8.46 (dd, J=4.6,1.5 Hz, 2H), 8.56-8.64 (m, 2H), 10.64 (s, 1H)

N-(3-Hydroxymethylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-40)

¹H-NMR (500 MHz, CDCl₃)

δ 3.49 (br s, 1H), 4.46 (s, 2H), 4.72 (s, 2H), 7.15 (dd, J=7.6, 4.5 Hz,1H), 7.18 (dd, J=7.6, 0.6 Hz, 1H), 7.34 (dd, J=4.5, 1.7 Hz, 2H), 7.37(d, J=7.6 Hz, 1H), 7.51 (d, J=7.6 Hz, 1H), 7.66 (s, 1H), 7.89-7.97 (m,2H), 8.49 (dd, J=4.5, 1.7 Hz, 2H), 8.55 (dd, J=4.9, 1.8 Hz, 1H)

N-(3-Isopropoxyphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-41)

¹H-NMR (500 MHz, CDCl₃)

δ 1.34 (d, J=6.1 Hz, 6H), 4.46 (s, 2H), 4.58 (m, 1H), 6.71 (dd, J=7.9,2.1 Hz, 1H), 7.04 (d, J=7.6 Hz, 1H), 7.14 (dd, J=7.6, 4.8 Hz, 1H), 7.24(m, 1H), 7.35 (m, 1H), 7.37 (dd, J=4.6, 1.5 Hz, 2H), 7.70-7.94 (m, 2H),8.50 (dd, J=4.6, 1.5 Hz, 2H), 8.53 (dd, J=4.8, 1.5 Hz, 1H)

2-(4-Pyridylmethylthio)-N-(3-trifluoromethoxyphenyl)pyridine-3-carboxamide(Compound No. 1-42)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.12 (dt, J=8.3, 1.2 Hz, 1H), 7.31 (dd, J=7.6, 4.9 Hz,1H), 7.41 (dd, J=4.4, 1.6 Hz, 2H), 7.49 (t, J=8.1 Hz, 1H), 7.64 (d,J=8.3 Hz, 1H), 7.86 (s, 1H), 8.01 (dd, J=7.6, 1.7 Hz, 1H), 8.46 (dd,J=4.4, 1.6 Hz, 2H), 8.67 (dd, J=1.7 Hz, 1H), 10.75 (s, 1H)

N-(3-Ethoxycarbonylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-43)

¹H-NMR (400 MHz, CDCl₃)

δ 1.39 (t, J=7.1 Hz, 3H), 4.38 (q, J=7.1 Hz, 2H), 4.46 (s, 2H), 7.15(dd, J=7.6, 4.9 Hz, 1H), 7.34 (dd, J=4.6, 1.5 Hz, 2H), 7.46 (dd, J=7.8Hz, 1H), 7.85 (dt, J=7.8, 1.5 Hz, 1H), 7.92 (dd, J=7.6, 1.7 Hz, 1H),8.04 (dt, J=7.8, 1.5 Hz, 1H), 8.09 (t, J=1.5 Hz, 1H), 8.20 (s, 1H), 8.47(dd, J=4.6, 1.5 Hz, 2H), 8.55 (dd, J=4.9, 1.7 Hz, 1H)

N-(4-Fluorophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-44)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.42 (s, 2H), 7.20 (td, J=8.9, 1.7 Hz, 2H), 7.30 (dd, J=7.6, 4.9 Hz,1H), 7.40 (dd, J=4.4, 1.5 Hz, 2H), 7.68-7.76 (m, 2H), 7.97 (dd, J=7.6,1.7 Hz, 1H), 8.45 (dd, J=4.4, 1.5 Hz, 2H), 8.59 (dd, J=4.9, 1.7 Hz, 1H),10.53 (s, 1H)

N-(4-Bromophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-45)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.42 (s, 2H), 7.30 (dd, J=7.6, 4.9 Hz, 1H), 7.40 (dd, J=4.5, 1.5 Hz,2H), 7.54 (d, J=8.8 Hz, 2H), 7.67 (d, J=8.8 Hz, 2H), 7.98 (dd, J=7.5,1.7 Hz, 1H), 8.45 (dd, J=4.5, 1.5 Hz, 2H), 8.60 (dd, J=4.9, 1.7 Hz, 1H),10.60 (s, 1H)

N-(4-Iodophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide (CompoundNo. 1-46)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.42 (s, 2H), 7.29 (dd, J=7.6, 4.8 Hz, 1H), 7.40 (dd, J=4.4, 1.5 Hz,2H), 7.53 (d, J=8.8 Hz, 2H), 7.69 (d, J=8.8 Hz, 2H), 7.97 (dd, J=7.6,1.8 Hz, 1H), 8.45 (dd, J=4.4, 1.5 Hz, 2H), 8.59 (dd, J=4.8, 1.8 Hz, 1H),10.57 (s, 1H)

N-(4-Methylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-47)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.27 (s, 3H), 4.41 (s, 2H), 7.15 (d, J=8.2 Hz, 2H), 7.28 (dd, J=7.6,4.8 Hz, 1H), 7.40 (dd, J=4.6, 1.5 Hz, 2H), 7.57 (d, J=8.2 Hz, 2H), 7.94(dd, J=7.6, 1.5 Hz, 1H), 8.45 (dd, J=4.6, 1.5 Hz, 2H), 8.58 (dd, J=4.8,1.5 Hz, 1H), 10.38 (s, 1H)

2-(4-Pyridylmethylthio)-N-(4-trifluoromethylphenyl)pyridine-3-carboxamide(Compound No. 1-48)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.32 (dd, J=7.6, 4.7 Hz, 1H), 7.40 (dd, J=4.4, 1.7 Hz,2H), 7.73 (d, J=8.6 Hz, 2H), 7.91 (d, J=8.6 Hz, 2H), 8.02 (dd, J=7.6,1.7 Hz, 1H), 8.45 (dd, J=4.4, 1.7 Hz, 2H), 8.61 (dd, J=4.7, 1.7 Hz, 1H),10.83 (s, 1H)

N-(4-n-Propylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-49)

¹H-NMR (500 MHz, DMSO-d₆)

δ 0.88 (t, J=7.3 Hz, 3H), 1.53-1.62 (m, 2H), 2.52 (t, J=7.6 Hz, 2H),4.41 (s, 2H), 7.16 (d, J=8.3 Hz, 2H), 7.28 (dd, J=7.6, 4.8 Hz, 1H), 7.40(dd, J=4.5, 1.4 Hz, 2H), 7.59 (d, J=8.3 Hz, 2H), 7.94 (dd, J=7.6, 1.5Hz, 1H), 8.45 (dd, J=4.5, 1.4 Hz, 2H), 8.58 (dd, J=4.8, 1.5 Hz, 1H),10.39 (s, 1H)

N-(4-n-Butylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-50)

¹H-NMR (500 MHz, CDCl₃)

δ 0.92 (t, J=7.3 Hz, 3H), 1.30-1.39 (m, 2H), 1.50-1.62 (m, 2H), 2.60 (t,J=7.6 Hz, 2H), 4.44 (s, 2H), 7.12 (dd, J=7.6, 4.9 Hz, 1H), 7.17 (d,J=8.1 Hz, 2H), 7.35 (dd, J=4.6, 1.8 Hz, 2H), 7.51 (d, J=8.1 Hz, 2H),7.88 (d, J=7.6 Hz, 1H), 8.00 (s, 1H), 8.49 (dd, J=4.6, 1.8 Hz, 2H), 8.51(dd, J=4.9, 1.5 Hz, 1H)

N-(4-tert-Butylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-51)

¹H-NMR (500 MHz, DMSO-d₆)

δ 1.27 (s, 9H), 4.41 (s, 2H), 7.28 (dd, J=7.6, 4.9 Hz, 1H), 7.36 (d,J=8.6 Hz, 2H), 7.40 (dd, J=4.3, 1.5 Hz, 2H), 7.60 (d, J=8.6 Hz, 2H),7.94 (dd, J=7.6, 1.5 Hz, 1H), 8.45 (dd, J=4.3, 1.5 Hz, 2H), 8.58 (dd,J=4.9, 1.5 Hz, 1H), 10.40 (s, 1H)

N-(4-n-Octylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-52)

¹H-NMR (500 MHz, CDCl₃)

δ 0.88 (t, J=7.0 Hz, 3H), 1.20-1.35 (m, 10H), 1.50-1.65 (m, 2H), 2.58(t, J=7.6 Hz, 2H), 4.45 (s, 2H), 7.13 (dd, J=7.6, 4.9 Hz, 1H), 7.18 (d,J=7.9 Hz, 2H), 7.34 (dd, J=4.3, 1.5 Hz, 2H), 7.51 (d, J=7.9 Hz, 2H),7.85-7.92 (m, 2H), 8.48 (dd, J=4.3, 1.5 Hz, 2H), 8.53 (dd, J=4.9, 1.8Hz, 1H)

N-(4-Methoxyphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-53)

¹H-NMR (400 MHz, DMSO-d₆)

δ 3.73 (s, 3H), 4.42 (s, 2H), 6.92 (d, J=9.0 Hz, 2H), 7.28 (dd, J=7.6,4.8 Hz, 1H), 7.44 (d, J=6.1 Hz, 2H), 7.60 (d, J=9.0 Hz, 2H), 7.95 (dd,J=7.6, 1.5 Hz, 1H), 8.47 (d, J=6.1 Hz, 2H), 8.57 (dd, J=4.8, 1.5 Hz,1H), 10.34 (s, 1H)

2-(4-Pyridylmethylthio)-N-(4-trifluoromethoxyphenyl)pyridine-3-carboxamide(Compound No. 1-54)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.42 (s, 2H), 7.30 (dd, J=7.6, 4.8 Hz, 1H), 7.37 (d, J=8.6 Hz, 2H),7.40 (dd, J=4.5, 1.2 Hz, 2H), 7.80 (d, J=8.6 Hz, 2H), 7.98 (dd, J=7.6,1.8 Hz, 1H), 8.45 (dd, J=4.5, 1.2 Hz, 2H), 8.60 (dd, J=4.8, 1.8 Hz, 1H),10.67 (s, 1H)

N-(4-Isopropoxyphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-55)

¹H-NMR (500 MHz, CDCl₃)

δ 1.33 (d, J=5.8 Hz, 6H), 4.45 (s, 2H), 4.52 (m, 1H), 6.89 (d, J=8.8 Hz,2H), 7.13 (dd, J=7.6, 4.9 Hz, 1H), 7.36 (dd, J=4.6, 1.5 Hz, 2H), 7.50(d, J=8.8 Hz, 2H), 7.85 (s, 1H), 7.89 (d, J=7.0 Hz, 1H), 8.50 (dd,J=4.6, 1.5 Hz, 2H), 8.52 (dd, J=4.9, 1.5 Hz, 1H)

N-(4-n-Butoxyphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-56)

¹H-NMR (500 MHz, CDCl₃)

δ 0.98 (t, J=7.3 Hz, 3H), 1.45-1.54 (m, 2H), 1.73-1.80 (m, 2H), 3.96 (t,J=6.4 Hz, 2H), 4.45 (s, 2H), 6.89 (d, J=8.5 Hz, 2H), 7.13 (dd, J=7.3,4.6 Hz, 1H), 7.34 (dd, J=4.3, 1.5 Hz, 2H), 7.50 (d, J=8.5 Hz, 2H), 7.85(s, 1H), 7.89 (d, J=7.3 Hz, 1H), 8.48 (dd, J=4.3, 1.5 Hz, 2H), 8.52 (dd,J=4.6, 1.5 Hz, 1H)

N-(4-Phenoxyphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-57)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.42 (s, 2H), 6.95-7.00 (m, 2H), 7.00-7.10 (m, 2H), 7.13 (m, 1H), 7.29(dd, J=7.3, 4.9 Hz, 1H), 7.35-7.45 (m, 4H), 7.71 (d, J=8.8 Hz, 2H), 7.98(m, 1H), 8.46 (dd, J=4.3, 1.5 Hz, 2H), 8.59 (m, 1H), 10.51 (s, 1H)

N-(4-Hydroxyphenyl)-2-(4-pyridylmethylthio)pyridine 3-carboxamide(Compound No. 1-58)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.40 (s, 2H), 6.73 (d, J=8.8 Hz, 2H), 7.27 (dd, J=7.8, 4.9 Hz, 1H),7.39 (d, J=6.1 Hz, 2H), 7.47 (d, J=8.8 Hz, 2H), 7.91 (dd, J=7.6, 1.5 Hz,1H), 8.42-8.50 (m, 2H), 8.56 (dd, J=4.9, 1.5 Hz, 1H), 9.29 (s, 1H),10.22 (s, 1H)

N-[4-(2-Hydroxyethyl)phenyl]-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-59)

¹H-NMR (500 MHz, CDCl₃)

δ 2.86 (t, J=6.4 Hz, 2H), 3.85 (t, J=6.4 Hz, 2H), 4.45 (s, 2H), 7.13(dd, J=7.5, 4.6 Hz, 1H), 7.23 (d, J=8.1 Hz, 2H), 7.33 (d, J=5.5 Hz, 2H),7.55 (d, J=8.1 Hz, 2H), 7.89 (dd, J=7.5, 1.8 Hz, 1H), 8.01 (br s, 1H),8.46 (br s, 2H) 8.53 (dd, J=4.6, 1.8 Hz, 1H)

N-(4-Isopropoxycarbonylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-60)

¹H-NMR (400 MHz, CDCl₃)

δ 1.37 (d, J=6.1 Hz, 6H), 4.46 (s, 2H), 5.25 (m, 1H), 7.16 (dd, J=7.6,4.6 Hz, 1H), 7.34 (dd, J=4.6, 1.4 Hz, 2H), 7.69 (d, J=8.8 Hz, 2H), 7.83(dd, J=7.6, 1.8 Hz, 1H), 8.04 (d, J=8.8 Hz, 2H), 8.18 (s, 1H), 8.47 (dd,J=4.6, 1.4 Hz, 2H), 8.56 (dd, J=4.6, 1.4 Hz, 1H)

N-(4-Ethoxycarbonylmethylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-61)

¹H-NMR (500 MHz, DMSO-d₆)

δ 1.18 (t, J=7.1 Hz, 3H), 3.62 (s, 2H), 4.07 (q, J=7.1 Hz, 2H), 4.41 (s,2H), 7.24 (d, J=8.5 Hz, 2H), 7.29 (dd, J=7.6, 4.9 Hz, 1H), 7.40 (dd,J=4.2, 1.5 Hz, 2H), 7.63 (d, J=8.5 Hz, 2H), 7.95 (dd, J=7.6, 1.5 Hz,1H), 8.45 (dd, J=4.2, 1.5 Hz, 2H), 8.59 (dd, J=4.9, 1.5 Hz, 1H), 10.47(s, 1H)

N-(4-Benzoylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-62)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.44 (s, 2H), 7.32 (dd, J=7.6, 4.8 Hz, 1H), 7.41 (dd, J=7.4, 1.5 Hz,2H), 7.55-7.60 (m, 2H), 7.68 (m, 1H), 7.73 (dd, J=8.2, 1.2 Hz, 2H), 7.79(d, J=8.8 Hz, 2H), 7.89 (d, J=8.8 Hz, 2H), 8.02 (dd, J=7.6, 1.8 Hz, 1H),8.46 (dd, J=4.2, 1.5 Hz, 2H), 8.62 (dd, J=4.8, 1.8 Hz, 1H), 10.86 (s,1H)

N-(4-Aminophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-63)

¹H-NMR (500 MHz, CDCl₃)

δ 3.65 (br s, 2H), 4.45 (s, 2H), 6.69 (d, J=8.6 Hz, 2H), 7.13 (dd,J=7.6, 4.9 Hz, 1H), 7.34 (d, J=4.6, 1.8 Hz, 2H), 7.38 (d, J=8.6 Hz, 2H),7.70 (s, 1H), 7.89 (d, J=7.6 Hz, 1H), 8.49 (dd, J=4.6, 1.8 Hz, 2H), 8.52(m, 1H)

N-(4-Dimethylaminophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-64)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.86 (s, 6H), 4.40 (s, 2H), 6.71 (dd, J=7.0, 2.1 Hz, 2H), 7.27 (dd,J=7.6, 4.9 Hz, 1H), 7.40 (dd, J=4.6, 1.5 Hz, 2H), 7.51 (dd, J=7.0, 2.1Hz, 2H), 7.92 (dd, J=7.6, 1.8 Hz, 1H), 8.45 (dd, J=4.6, 1.5 Hz, 2H),8.56 (dd, J=4.9, 1.8 Hz, 1H), 10.17 (s, 1H)

N-(3-Methylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-65)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.30 (s, 3H), 4.42 (s, 2H), 6.93 (d, J=7.6 Hz, 1H), 7.23 (dd, J=8.1,7.6 Hz, 1H), 7.28 (dd, J=7.6, 4.6 Hz, 1H), 7.40 (dd, J=4.4, 1.5 Hz, 2H),7.46 (d, J=8.1 Hz, 1H), 7.56 (s, 1H), 7.94 (dd, J=7.6, 1.7 Hz, 1H), 8.45(dd, J=4.4, 1.7 Hz, 2H), 8.58 (dd, J=4.6, 1.7 Hz, 1H), 10.40 (s, 1H)

N-(4-Acetylaminophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-66)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.03 (s, 3H), 4.41 (s, 2H), 7.28 (dd, J=7.6, 4.6 Hz, 1H), 7.40 (d,J=5.9 Hz, 2H), 7.54 (d, J=9.0 Hz, 2H), 7.60 (d, J=9.0 Hz, 2H), 7.95 (m,1H), 8.43-8.50 (m, 2H), 8.58 (dd, J=4.6, 1.4 Hz, 1H), 9.93 (s, 1H),10.41 (s, 1H)

N-(4-Morpholinophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-67)

¹H-NMR (500 MHz, DMSO-d₆)

δ 3.06 (t, J=4.8 Hz, 4H), 3.74 (t, J=4.8 Hz, 4H), 4.41 (s, 2H), 6.93 (d,J=9.0 Hz, 2H), 7.27 (dd, J=7.6, 4.9 Hz, 1H), 7.40 (dd, J=4.7, 1.5 Hz,2H), 7.56 (d, J=9.0 Hz, 2H), 7.93 (dd, J=7.6, 1.8 Hz, 1H), 8.45 (dd,J=4.7, 1.5 Hz, 2H), 8.57 (dd, J=4.9, 1.8 Hz, 1H), 10.27 (br, 1H)

N-(2,3-Dimethylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-68)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.13 (s, 3H), 2.27 (s, 3H), 4.42 (s, 2H), 7.05-7.20 (m, 3H), 7.30 (m,1H), 7.41 (dd, J=4.3, 1.5 Hz, 2H), 8.01 (m, 1H), 8.46 (dd, J=4.3, 1.5Hz, 2H), 8.59 (m, 1H), 10.03 (s, 1H)

N-(4-Chloro-2-fluorophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-69)

¹H-NMR (500 MHz, CDCl₃)

δ 4.46 (s, 2H), 7.15-7.20 (m, 3H), 7.34 (dd, J=4.6, 1.5 Hz, 2H), 7.93(dd, J=7.6, 1.8 Hz, 1H), 8.18 (s, 1H), 8.43 (m, 1H), 8.49 (dd, J=4.6,1.5 Hz, 2H), 8.56 (dd, J=4.6, 1.8 Hz, 1H)

N-(2,4-Difluorophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-70)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.41 (s, 2H), 7.13 (m, 1H), 7.30 (dd, J=7.7, 4.9 Hz, 1H), 7.35 (m,1H), 7.41 (dd, J=4.5, 1.4 Hz, 2H), 7.68 (m, 1H), 8.02 (m, 1H), 8.46 (dd,J=4.5, 1.4 Hz, 2H), 8.60 (dd, J=4.9, 1.5 Hz, 1H), 10.33 (s, 1H)

N-(2,6-Diisopropylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-71)

¹H-NMR (400 MHz, DMSO-d₆)

δ 1.14 (d, J=6.6 Hz, 12H), 3.18 (m, 2H), 4.43 (s, 2H), 7.19 (d, J=7.6Hz, 2H) 7.25-7.35 (m, 2H), 7.41 (d, J=5.8 Hz, 2H), 7.95 (m, 1H), 8.47(d, J=5.8 Hz, 2H), 8.60 (m, 1H), 9.86 (s, 1H)

N-(3,4-Dimethoxyphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-72)

¹H-NMR (500 MHz, DMSO-d₆)

δ 3.73 (s, 6H), 4.41 (s, 2H), 6.93 (d, J=8.8 Hz, 1H), 7.22 (dd, J=8.8,2.4 Hz, 1H), 7.28 (dd, J=7.3 4.8 Hz, 1H), 7.38-7.41 (m, 3H), 7.95 (dd,J=7.6, 1.5 Hz, 1H), 8.43-8.47 (m, 2H), 8.57 (dd, J=4.8, 1.5 Hz, 1H),10.31 (s, 1H)

N-(3,4-Difluorophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-73)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.42 (s, 2H), 7.31 (dd, J=7.8, 4.6 Hz, 1H), 7.40-7.50 (m, 4H), 7.85(m, 1H), 7.99 (dd, J=7.8, 1.7 Hz, 1H), 8.45 (d, J=4.4, 1.7 Hz, 2H), 8.60(dd, J=4.6, 1.7 Hz, 1H), 10.70 (s, 1H)

N-(4-Chloro-3-trifluoromethylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-74)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.32 (dd, J=7.6, 4.9 Hz, 1H), 7.40 (d, J=5.9 Hz, 2H),7.73 (d, J=8.8 Hz, 1H), 7.97 (dd, J=8.8, 2.4 Hz, 1H), 8.04 (dd, J=7.6,1.7 Hz, 1H), 8.28 (d, J=2.4 Hz, 1H), 8.45 (d, J=5.9 Hz, 2H), 8.62 (dd,J=4.9, 1.7 Hz, 1H), 10.89 (s, 1H)

N-(3-Chloro-4-fluorophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-75)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.42 (s, 2H), 7.31 (dd, J=7.7, 4.9 Hz, 1H), 7.40 (dd, J=4.3, 1.5 Hz,2H), 7.44 (t, J=9.2 Hz, 1H), 7.61 (m, 1H), 7.96-8.04 (m, 2H), 8.46 (dd,J=4.3, 1.5 Hz, 2H), 8.61 (dd, J=4.9, 1.5 Hz, 1H), 10.68 (s, 1H)

N-(3,4-Dichlorophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-76)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.42 (s, 2H), 7.31 (dd, J=7.6, 4.9 Hz, 1H), 7.40 (dd, J=4.4, 1.5 Hz,2H), 7.62 (d, J=1.2 Hz, 2H), 8.00 (dd, J=7.6, 1.7 Hz, 1H), 8.07 (t,J=1.2 Hz, 1H), 8.45 (dd, J=4.4, 1.5 Hz, 2H), 8.61 (dd, J=4.9, 1.7 Hz,1H), 10.70 (s, 1H)

N-(4-Fluoro-3-trifluoromethylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-77)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.42 (s, 2H), 7.32 (dd, J=7.6, 4.9 Hz, 1H), 7.40 (dd, J=4.4, 1.7 Hz,2H), 7.54 (m, 1H), 7.97 (m, 1H), 8.03 (dd, J=7.6, 1.7 Hz, 1H), 8.19 (m,1H), 8.46 (dd, J=4.4, 1.7 Hz, 2H), 8.62 (dd, J=4.9, 1.7 Hz, 1H), 10.81(s, 1H)

N-(3-Chloro-4-methylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-78)

¹H-NMR (500 MHz, CDCl₃)

δ 2.35 (s, 3H), 4.46 (s, 2H), 7.14 (dd, J=7.6, 4.6 Hz, 1H), 7.20 (d,J=8.2 Hz, 1H), 7.35 (dd, J=4.5, 1.5 Hz, 2H), 7.37 (m, 1H), 7.72 (s, 1H),7.89 (dd, J=7.6, 1.5 Hz, 1H), 8.02 (m, 1H), 8.48 (dd, J=4.5, 1.5 Hz,2H), 8.54 (dd, J=4.9, 1.5 Hz, 1H)

N-(4-Chloro-3-methylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-79)

¹H-NMR (500 MHz, CDCl₃)

δ 2.39 (s, 3H), 4.46 (s, 2H), 7.15 (dd, J=7.6, 4.9 Hz, 1H), 7.33 (m,1H), 7.35 (dd, J=4.5, 1.5 Hz, 2H), 7.37 (m, 1H), 7.56 (s, 1H), 7.90 (d,J=6.4 Hz, 1H), 8.01 (s, 1H), 8.50 (dd, J=4.5, 1.5 Hz, 2H), 8.55 (dd,J=4.9, 1.8 Hz, 1H)

N-(3,4-Dimethylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-80)

¹H-NMR (500 MHz, CDCl₃)

δ 2.24 (s, 3H), 2.27 (s, 3H), 4.45 (s, 2H), 7.09-7.16 (m, 2H), 7.30 (m,1H), 7.35 (dd, J=4.6, 1.5 Hz, 2H), 7.43 (m, 1H), 7.83 (s, 1H), 7.88 (d,J=7.0 Hz, 1H), 8.49 (dd, J=4.6, 1.5 Hz, 2H), 8.52 (dd, J=4.9, 1.8 Hz,1H)

N-(4-Bromo-3-methylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-81)

¹H-NMR (500 MHz, CDCl3)

δ 2.41 (s, 3H), 4.46 (s, 2H), 7.15 (dd, J=7.6, 4.9 Hz, 1H), 7.29 (m,1H), 7.35 (dd, J=4.3, 1.5 Hz, 2H), 7.50 (d, J=8.6 Hz, 1H), 7.57 (s, 1H),7.88-7.94 (m, 2H), 8.50 (dd, J=4.3, 1.5 Hz, 2H), 8.55 (dd, J=4.9, 1.8Hz, 1H)

N-(3-Hydroxy-4-methylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-82)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.07 (s, 3H), 4.41 (s, 2H), 6.94 (d, J=8.3 Hz, 1H), 6.98 (d, J=8.3 Hz,1H), 7.27 (dd, J=7.8, 4.9 Hz, 1H), 7.35 (s, 1H), 7.40 (dd, J=4.4, 1.5Hz, 2H), 7.91 (dd, J=7.8, 1.9 Hz, 1H), 8.45 (dd, J=4.4, 1.5 Hz, 2H),8.57 (dd, J=4.9, 1.9 Hz, 1H), 9.36 (s, 1H), 10.27 (s, 1H)

N-(3-Fluoro-5-trifluoromethylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-83)

¹H-NMR (400 MHz, CDCl₃)

δ 4.48 (s, 2H), 7.10-7.20 (m, 2H), 7.33 (dd, J=4.6, 1.5 Hz, 2H), 7.55(s, 1H), 7.83 (d, J=8.2 Hz, 1H), 7.92 (dd, J=7.6, 1.8 Hz, 1H), 8.38 (s,1H), 8.45 (d, J=5.9 Hz, 2H), 8.57 (dd, J=5.9, 1.8 Hz, 1H)

N-(3,5-Dichlorophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-84)

¹H-NMR (500 MHz, CDCl₃)

δ 4.47 (s, 2H), 7.14-7.18 (m, 2H), 7.33 (d, J=5.8 Hz, 2H), 7.59 (d,J=1.5 Hz, 2H), 7.89 (dd, J=7.6, 1.8 Hz, 1H), 8.14 (s, 1H), 8.47 (d,J=5.8 Hz, 2H), 8.55 (dd, J=4.9, 1.8 Hz, 1H)

N-(5-Chloro-2,4-dimethoxyphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-85)

¹H-NMR (400 MHz, DMSO-d₆)

δ 3.86 (s, 3H), 3.90 (s, 3H), 4.40 (s, 2H), 6.87 (s, 1H), 7.26 (dd,J=7.1, 4.4 Hz, 1H), 7.40 (d, J=4.5, 1.7 Hz, 2H), 7.76 (s, 1H), 7.96 (d,J=7.1 Hz, 1H), 8.46 (dd, J=4.5, 1.7 Hz, 2H), 8.57 (d, J=2.9 Hz, 1H),9.73 (s, 1H)

2-(4-Pyridylmethylthio)-N-(3,4,5-trimethoxyphenyl)pyridine-3-carboxamide(Compound No. 1-86)

¹H-NMR (400 MHz, DMSO-d₆)

δ 3.63 (s, 3H), 3.75 (s, 6H), 4.41 (s, 2H), 7.12 (s, 2H), 7.29 (dd,J=7.6, 4.8 Hz, 1H), 7.39-7.41 (m, 2H), 7.95 (dd, J=7.6, 1.6 Hz, 1H),8.44-8.47 (m, 2H), 8.59 (dd, J=4.8, 1.6 Hz, 1H), 10.39 (s, 1H)

N-(4-Chlorophenyl)-2-(4-pyridylmethylthio)benzamide (Compound No. 1-87)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.26 (s, 2H), 7.29 (td, J=7.5, 1.2 Hz, 1H), 7.36 (dd, J=4.5, 1.6 Hz,2H), 7.40-7.55 (m, 3H), 7.47 (dd, J=8.0, 0.9 Hz, 1H), 7.52 (dd, J=7.5,1.2 Hz, 1H), 7.76 (d, J=8.7 Hz, 2H), 8.45 (dd, J=4.5, 1.6 Hz, 2H), 10.51(s, 1H)

N-(4-Methoxyphenyl)-2-(4-pyridylmethylthio)benzamide (Compound No. 1-88)

¹H-NMR (400 MHz, DMSO-d₆)

δ 3.74 (s, 3H), 4.25 (s, 2H), 6.92 (d, J=9.0 Hz, 2H), 7.28 (m, 1H),7.30-7.50 (m, 5H), 7.63 (d, J=9.0 Hz, 2H), 8.40-8.50 (m, 2H), 10.22 (s,1H)

N-(4-tert-Butylphenyl)-2-(4-pyridylmethylthio)benzamide (Compound No.1-89)

¹H-NMR (400 MHz, DMSO-d₆)

δ 1.27 (s, 9H), 4.25 (s, 2H), 7.26-7.52 (m, 8H), 7.63 (d, J=9.5 Hz, 2H),8.45 (dd, J=4.4, 1.5 Hz, 2H), 10.28 (s, 1H)

N-(3-Chlorophenyl)-2-(4-pyridylmethylthio)benzamide (Compound No. 1-90)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.26 (s, 2H), 7.16 (ddd, J=8.2, 2.1, 0.9 Hz, 1H), 7.30 (td, J=7.8, 1.2Hz, 1H), 7.35 (d, J=4.3 Hz, 2H), 7.38 (d, J=8.2 Hz, 1H), 7.43 (td,J=7.8, 1.5 Hz, 1H), 7.47 (dd, J=7.8, 0.9 Hz, 1H), 7.53 (dd, J=7.8, 1.5Hz, 1H), 7.60 (d, J=8.2 Hz, 1H), 7.92 (s, 1H), 8.45 (dd, J=4.3, 1.5 Hz,2H), 10.54 (s, 1H)

N-(4-Dimethylaminophenyl)-2-(4-pyridylmethylthio)benzamide (Compound No.1-91)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.86 (s, 6H), 4.24 (s, 2H), 6.71 (d, J=8.8 Hz, 2H), 7.27 (td, J=7.5,1.2 Hz, 1H), 7.37 (m, 3H), 7.43 (d, J=7.5 Hz, 1H), 7.48 (dd, J=7.5, 1.9Hz, 1H), 7.53 (d, J=8.8 Hz, 2H), 8.46 (dd, J=4.6, 1.5 Hz, 2H), 10.03 (s,1H)

N-(3-Isopropylphenyl)-2-(4-pyridylmethylthio)benzamide (Compound No.1-92)

¹H-NMR (400 MHz, DMSO-d₆)

δ 1.20 (d, J=7.1 Hz, 6H), 2.85 (m, 1H), 4.25 (s, 2H), 6.98 (d, J=7.6 Hz,1H), 7.21-7.33 (m, 2H), 7.36 (dd, J=4.4, 1.5 Hz, 2H), 7.37-7.48 (m, 2H),7.49-7.57 (m, 2H), 7.63 (s, 1H), 8.45 (dd, J=4.4, 1.5 Hz, 2H), 10.28 (s,1H)

N-(3,4-Dimethoxyphenyl)-2-(4-pyridylmethylthio)benzamide (Compound No.1-93)

¹H-NMR (400 MHz, DMSO-d₆)

δ 3.73 (s, 6H), 4.25 (s, 2H), 6.92 (d, J=8.5 Hz, 1H), 7.20-7.30 (m, 2H),7.30-7.55 (m, 6H), 8.46 (d, J=6.1 Hz, 2H), 10.21 (s, 1H)

2-(4-Pyridylmethylthio)-N-(3,4,5-trimethoxyphenyl)benzamide (CompoundNo. 1-94)

¹H-NMR (400 MHz, DMSO-d₆)

δ 3.63 (s, 3H), 3.75 (s, 6H), 4.26 (s, 2H), 7.16 (s, 2H), 7.29 (dd,J=7.3, 1.2 Hz, 1H), 7.34 (dd, J=4.4, 1.7 Hz, 2H), 7.35-7.55 (m, 3H),8.46 (d, J=4.4, 1.7 Hz, 2H), 10.26 (s, 1H)

2-(4-Pyridylmethylthio)-N-(3-quinolyl)benzamide (Compound No. 1-95)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.29 (s, 2H), 7.30-7.70 (m, 8H), 7.98 (d, J=8.3 Hz, 2H), 8.46 (dd,J=4.4, 1.5 Hz, 2H), 8.86 (s, 1H), 9.02 (d, J=2.2 Hz, 1H), 10.86 (s, 1H)

N-(4-Chlorophenyl)-5-fluoro-2-(4-pyridylmethylthio)benzamide (CompoundNo. 1-96)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.22 (s, 2H), 7.28 (m, 1H), 7.29 (dd, J=4.4, 1.7 Hz, 2H), 7.42 (dd,J=8.8, 2.0 Hz, 2H), 7.43-7.50 (m, 2H), 7.74 (d, J=8.8 Hz, 2H), 8.44 (dd,J=4.4, 1.7 Hz, 2H), 10.50 (s, 1H)

N-(4-Chlorophenyl)-4-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-97)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.39 (s, 2H), 7.42 (d, J=8.8 Hz, 2H), 7.46 (dd, J=4.6, 1.5 Hz, 2H),7.51 (d, J=5.4 Hz, 1H), 7.74 (d, J=8.8 Hz, 2H), 8.50 (d, J=5.4 Hz, 1H),8.51 (dd, J=4.6, 1.5 Hz, 2H), 8.67 (s, 1H), 10.70 (s, 1H)

N-(4-Chlorophenyl)-3-(4-pyridylmethylthio)pyridine-2-carboxamide(Compound No. 1-98)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.31 (s, 2H), 7.41 (dd, J=8.8, 2.0 Hz, 2H), 7.46 (dd, J=4.4, 1.5 Hz,2H), 7.56 (dd, J=8.2, 4.5 Hz, 1H), 7.88 (d, J=8.8 Hz, 2H), 7.98 (dd,J=8.2, 1.3 Hz, 1H), 8.46 (dd, J=4.5, 1.3 Hz, 1H), 8.51 (dd, J=4.4, 1.5Hz, 2H), 10.75 (s, 1H)

N-(4-Chloro-3-methylphenyl)-2-(4-pyridylmethylthio)benzamide (CompoundNo. 1-99)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.32 (s, 3H), 4.26 (s, 2H), 7.27-7.58 (m, 8H), 7.76 (s, 1H), 8.46 (dd,J=4.4, 1.7 Hz, 2H), 10.40 (s, 1H)

N-(3-Chloro-4-methylphenyl)-2-(4-pyridylmethylthio)benzamide (CompoundNo. 1-100)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.30 (s, 3H), 4.25 (s, 2H), 7.28-7.53 (m, 8H), 7.91 (d, J=1.5 Hz, 1H),8.45 (dd, J=5.7, 1.7 Hz, 2H), 10.40 (s, 1H)

N-(2,3-Dimethylphenyl)-2-(4-pyridylmethylthio)benzamide (Compound No.1-101)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.16 (s, 3H), 2.27 (s, 3H), 4.27 (s, 2H), 7.06-7.47 (m, 8H), 7.57 (m,1H), 8.47 (dd, J=4.5, 1.6 Hz, 2H), 9.86 (s, 1H)

N-(5-Chloro-2,4-dimethoxyphenl)-2-(4-pyridylmethylthio)benzamide(Compound No. 1-102)

¹H-NMR (500 MHz, DMSO-d₆)

δ 3.87 (s, 3H), 3.90 (s, 3H), 4.25 (s, 2H), 6.88 (s, 1H), 7.28 (t, J=7.2Hz, 1H), 7.36 (dd, J=4.3, 1.5 Hz, 2H), 7.37-7.43 (m, 2H), 7.56 (d, J=7.2Hz, 1H), 7.84 (s, 1H), 8.46 (dd, J=4.3, 1.5 Hz, 2H), 9.48 (s, 1H)

N-(3-Bromophenyl)-2-(4-pyridylmethylthio)benzamide (Compound No. 1-103)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.26 (s, 2H), 7.28-7.48 (m, 7H), 7.53 (dd, J=7.6, 1.2 Hz, 1H), 7.64(d, J=7.3 Hz, 1H), 8.07 (s, 1H), 8.45-8.46 (m, 2H), 10.53 (s, 1H)

N-(3,5-Dimethylphenyl)-2-(4-pyridylmethylthio)benzamide (Compound No.1-104)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.25 (s, 6H), 4.25 (s, 2H), 6.74 (s, 1H), 7.28 (dt, J=7.3, 1.2 Hz,1H), 7.35-7.49 (m, 7H), 8.45-8.46 (m, 2H), 10.19 (s, 1H)

N-(3-Dimethylaminophenyl)-2-(4-pyridylmethylthio)benzamide (Compound No.1-105)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.88 (s, 6H), 4.25 (s, 2H), 6.48 (dd, J=8.1, 1.7 Hz, 1H), 7.06-7.13(m, 2H), 7.17 (s, 1H), 7.26-7.50 (m, 6H), 8.45-8.46 (m, 2H), 10.13 (s,1H)

N-(3,5-Dimethylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-106)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.50 (s, 6H), 4.41 (s, 2H), 6.76 (s, 1H), 7.28 (dd, J=7.6, 4.9 Hz,1H), 7.32 (s, 2H), 7.39-7.40 (m, 2H), 7.92 (dd, J=7.6, 1.8 Hz, 1H),8.45-8.46 (m, 2H), 8.57-8.58 (m, 1H), 10.30 (s, 1H)

N-(3-Dimethylaminophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-107)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.88 (s, 6H), 4.41 (s, 2H), 6.49 (m, 1H), 7.03 (d, J=7.9 Hz, 1H),7.11-7.14 (m, 2H), 7.28 (dd, J=7.6, 4.9 Hz, 1H), 7.39-7.41 (m, 2H), 7.93(dd, J=7.6, 1.5 Hz, 1H), 8.44-8.46 (m, 2H), 8.57 (dd, J=4.9, 1.8 Hz,1H), 10.25 (s, 1H)

N-(4-Bromo-3-trifluoromethylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-108)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.32 (dd, J=7.6, 4.6 Hz, 1H), 7.40 (dd, J=7.4, 1.5 Hz,2H), 7.85-7.93 (m, 2H), 8.04 (dd, J=7.6, 1.7 Hz, 1H), 8.27 (d, J=1.7 Hz,1H), 8.46 (dd, J=4.4, 1.5 Hz, 2H), 8.62 (dd, J=4.6, 1.7 Hz, 1H), 10.88(s, 1H)

N-(4-Fluoro-3-methylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-109)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.23 (s, 3H), 4.42 (s, 2H), 7.12 (t, J=9.3 Hz, 1H), 7.29 (dd, J=7.6,4.9 Hz, 1H), 7.40 (dd, J=4.4, 1.7 Hz, 2H), 7.46-7.53 (m, 1H), 7.63 (dd,J=6.8, 2.2 Hz, 1H), 7.95 (dd, J=7.6, 1.7 Hz, 1H), 8.45 (dd, J=4.4, 1.7Hz, 2H), 8.59 (dd, J=4.9, 1.7 Hz, 1H), 10.44 (s, 1H)

N-(3-Fluoro-4-methylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-110)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.23 (d, J=1.7 Hz, 3H), 4.42 (s, 2H), 7.12 (t, J=9.1 Hz, 1H), 7.29(dd, J=7.6, 4.8 Hz, 1H), 7.40 (dd, J=4.4, 1.7 Hz, 2H), 7.49 (m, 1H),7.63 (dd, J=6.8, 2.2 Hz, 1H), 7.95 (dd, J=7.6, 1.7 Hz, 1H), 8.46 (dd,J=4.4, 1.7 Hz, 2H), 8.59 (dd, J=4.8, 1.7 Hz, 1H), 10.45 (s, 1H)

N-(4-Bromo-3-methylphenyl)-2-(4-pyridylmethylthio)benzamide (CompoundNo. 1-111)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.34 (s, 3H), 4.25 (s, 2H), 7.29 (ddd, J=7.6, 7.3, 0.9 Hz, 1H), 7.35(dd, J=4.6, 1.5 Hz, 2H), 7.41 (ddd, J=8.2, 7.6, 1.5 Hz, 1H), 7.44-7.56(m, 4H), 7.75 (s, 1H), 8.45 (dd, J=4.6, 1.5 Hz, 2H), 10.42 (s, 1H)

N-(4-n-Propylphenyl)-2-(4-pyridylmethylthio)benzamide (Compound No.1-112)

¹H-NMR (500 MHz, DMSO-d₆)

δ 0.89 (t, J=7.3 Hz, 3H), 1.57 (dt, J=7.6, 7.3 Hz, 2H), 2.52 (t, J=7.6Hz, 2H), 4.25 (s, 2H), 7.15 (d, J=8.2 Hz, 2H), 7.28 (ddd, J=7.6, 7.3,0.9 Hz, 1H), 7.36 (dd, J=4.6, 1.5 Hz, 2H); 7.40 (ddd, J=7.9, 7.6, 0.9Hz, 1H), 7.45 (dd, J=7.9, 0.9 Hz, 1H), 7.50 (d, J=6.7 Hz, 1H), 7.62 (d,J=8.2 Hz, 2H), 8.45 (dd, J=4.6, 1.5 Hz, 2H), 10.27 (s, 1H)

N-(4-Methyl-3-nitrophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-113)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.50 (s, 3H), 4.42 (s, 2H), 7.32 (dd, J=7.6, 4.9 Hz, 1H), 7.40 (dd,J=4.4, 1.7 Hz, 2H), 7.50 (d, J=8.3 Hz, 1H), 7.85 (dd, J=8.3, 2.2 Hz,1H), 8.03 (dd, J=7.6, 1.7 Hz, 1H), 8.45 (dd, J=4.4, 1.5 Hz, 2H), 8.48(d, J=2.2 Hz, 1H), 8.61 (dd, J=4.9, 1.7 Hz, 1H), 10.83 (s, 1H)

2-(4-Pyridylmethylthio)-N-(3-trifluoromethylphenyl)pyridine-3-carboxamide(Compound No. 1-114)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.32 (dd, J=7.6, 4.9 Hz, 1H), 7.41 (dd, J=4.4, 1.5 Hz,2H), 7.48 (d, J=7.6 Hz, 1H), 7.61 (t, J=8.1 Hz, 1H), 7.91 (d, J=8.1 Hz,1H), 8.03 (dd, J=7.6, 1.7 Hz, 1H), 8.19 (s, 1H), 8.46 (dd, J=4.4, 1.5Hz, 2H), 8.62 (dd, J=4.9, 1.7 Hz, 1H), 10.81 (s, 1H)

N-[3-(1-Ethynyl)phenyl]-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-115)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.21 (s, 1H), 4.23 (s, 2H), 7.23 (dt, J=7.6, 1.2 Hz, 1H), 7.30 (dd,J=7.8, 4.9 Hz, 1H), 7.36 (t, J=8.1 Hz, 1H), 7.40 (dd, J=4.4, 1.7 Hz,2H), 7.69 (d, J=8.1 Hz, 1H), 7.87 (s, 1H), 7.98 (dd, J=7.6, 1.7 Hz, 1H),8.45 (dd, J=4.4, 1.7 Hz, 2H), 8.60 (dd, J=4.9, 1.7 Hz, 1H), 10.57 (s,1H)

N-[4-(N′-n-Propylureido)phenyl]-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-116)

¹H-NMR (400 MHz, DMSO-d₆)

δ 0.87 (t, J=7.3 Hz, 3H), 1.43 (q, J=7.3 Hz, 2H), 3.00-3.06 (m, 2H),4.40 (s, 2H), 6.13 (m, 1H), 7.26 (d, J=4.9 Hz, 2H), 7.25-7.40 (m, 3H),7.40 (d, J=4.6 Hz, 2H), 7.53 (d, J=8.8 Hz, 2H), 7.93 (dd, J=7.6, 1.5 Hz,1H), 8.45 (d, J=5.9 Hz, 2H), 10.30 (s, 1H)

4-Chloro-N-(4-chlorophenyl)-2-(4-pyridylmethylthio)benzamide (CompoundNo. 1-117)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.81 (s, 2H), 7.28-7.33 (m, 4H), 7.39 (dd, J=5.2, 2.4 Hz, 1H), 7.52(dd, J=8.6, 2.4 Hz, 1H), 7.58 (dd, J=6.8, 1.8 Hz, 2H), 8.27 (d, J=8.6Hz, 1H), 8.60 (dd, J=4.6, 1.5 Hz, 2H), 10.07 (s, 1H)

N-(2,2-Dimethylpropyl)-2-(4-pyridylmethylthio)benzamide (Compound No.1-118)

¹H-NMR (400 MHz, DMSO-d₆)

δ 0.91 (s, 9H), 3.04 (d, J=6.4 Hz, 2H), 4.22 (s, 2H), 7.21 (td, J=7.3,1.7 Hz, 1H), 7.34 (m, 5H), 8.29 (t, J=6.4 Hz, 1H), 8.46 (dd, J=4.4, 1.8Hz, 2H)

N-(3-tert-Butylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-119)

¹H-NMR (500 MHz, DMSO-d₆)

δ 1.28 (s, 9H), 4.42 (s, 2H), 7.15 (ddd, J=7.6, 1.8, 0.9 Hz, 1H),7.25-7.30 (m, 2H), 7.40 (dd, J=4.5, 1.6 Hz, 2H), 7.57 (d, J=7.9 Hz, 1H),7.71 (s, 1H), 7.96 (dd, J=7.6, 1.8 Hz, 1H), 8.45 (dd, J=4.5, 1.6 Hz,2H), 8.58 (dd, J=4.8, 1.8 Hz, 1H), 10.39 (s, 1H)

2-(4-Pyridylmethylthio)-N-(3-trifluoromethoxyphenyl)benzamide (CompoundNo. 1-120)

¹H-NMR (500 CDCl₃)

δ 4.03 (s, 2H), 7.03 (ddd, J=7.0, 2.0, 0.9 Hz, 1H), 7.08 (dd, J=4.6, 1.8Hz, 2H), 7.32-7.40 (m, 4H), 7.47 (d, J=7.6 Hz, 1H), 7.68 (s, 1H), 7.74(dd, J=7.0, 0.9 Hz, 1H), 8.42 (dd, J=4.6, 1.8 Hz, 2H), 8.48 (s, 1H)

2-(4-Pyridylmethylthio)-N-(4-trifluoromethoxyphenyl)benzamide (CompoundNo. 1-121)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.26 (s, 2H), 7.30 (td, J=7.3, 1.2 Hz, 1H), 7.33-7.38 (m, 4H), 7.43(td, J=7.1, 1.5 Hz, 1H), 7.48 (dd, J=8.0, 1.1 Hz, 1H), 7.53 (dd, J=7.6,1.5 Hz, 1H), 7.83 (d, J=9.0 Hz, 2H), 8.45 (dd, J=4.4, 1.7 Hz, 2H), 10.56(s, 1H)

N-(3,5-Di-tert-butylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-122)

¹H-NMR (400 MHz, DMSO-d₆)

δ 1.28 (s, 18H), 4.41 (s, 2H), 7.16 (t, J=1.7 Hz, 1H), 7.28 (dd, J=7.6,4.9 Hz, 1H), 7.39-7.41 (m, 2H), 7.59 (d, J=1.2 Hz, 2H), 7.96 (dd, J=7.6,1.5 Hz, 1H), 8.45 (dd, J=4.4, 1.7 Hz, 2H), 8.58 (dd, J=4.9, 1.7 Hz, 1H),10.33 (s, 1H)

N-(3,5-Dimethoxycarbonylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-123)

¹H-NMR (500 MHz, DMSO-d₆)

δ 3.91 (s, 6H), 4.43 (s, 2H), 7.32 (dd, J=7.6, 4.9 Hz, 1H), 7.41 (dd,J=4.4, 1.7 Hz, 2H), 8.08 (dd, J=7.7, 1.8 Hz, 1H), 8.23 (t, J=1.5 Hz,1H), 8.46 (dd, J=4.4, 1.7 Hz, 2H), 8.61-8.62 (m, 3H), 10.89 (s, 1H)

N-(3,5-Dichlorophenyl)-2-(4-pyridylmethylthio)benzamide (Compound No.1-124)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.26 (s, 2H), 7.29-7.78 (m, 7H), 7.80 (d, J=1.7 Hz, 2H), 8.46 (dd,J=5.4, 1.7 Hz, 2H), 10.70 (s, 1H)

N-(3-Chloro-4-fluorophenyl)-2-(4-pyridylmethylthio)benzamide (CompoundNo. 1-125)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.26 (s, 2H), 7.28-7.64 (m, 8H), 8.04 (dd, J=6.8, 2.4 Hz, 1H), 8.46(dd, J=4.4, 1.5 Hz, 2H), 10.58 (s, 1H)

N-(3-Methoxy-5-trifluoromethylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-126)

¹H-NMR (500 MHz, DMSO-d₆)

δ 3.83 (s, 3H), 4.43 (s, 2H), 7.01 (d, J=1.5 Hz, 1H), 7.32 (dd, J=7.6,4.9 Hz, 1H), 7.40 (dd, J=4.3, 1.5 Hz, 2H), 7.57 (s, 1H), 7.74 (s, 1H),8.02 (dd, J=7.6, 1.8 Hz, 1H), 8.45 (dd, J=4.3, 1.5 Hz, 2H), 8.62 (dd,J=4.9, 1.8 Hz, 1H), 10.74 (s, 1H)

N-[3,5-Bis(trifluoromethyl)phenyl]2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-127)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.35 (dd, J=7.8, 4.8 Hz, 1H), 7.41 (dd, J=4.6, 1.5 Hz,2H), 7.86 (s, 1H), 8.10 (dd, J=7.8, 1.8 Hz, 1H), 8.39 (s, 2H), 8.46 (dd,J=4.6, 1.5 Hz, 2H), 8.64 (dd, J=4.8, 1.8 Hz, 1H), 11.08 (s, 1H)

N-(4-Nitrophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-128)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.32 (dd, J=7.8, 4.9 Hz, 1H), 7.40 (dd, J=4.4, 1.7 Hz,2H), 7.96 (d, J=9.1 Hz, 2H), 8.05 (dd, J=7.6, 1.7 Hz, 1H), 8.28 (d,J=9.1 Hz, 2H), 8.45 (dd, J=4.4, 1.7 Hz, 2H), 8.63 (dd, J=4.9, 1.7 Hz,1H), 11.05 (s, 1H)

N-(3,5-Dibenzyloxycarbonylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-129)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.42 (s, 2H), 5.40 (s, 4H), 7.31 (dd, J=7.6, 4.9 Hz, 1H), 7.35-7.49(m, 12H), 8.05 (dd, J=7.6, 1.8 Hz, 1H), 8.28 (t, J=1.6 Hz, 1H), 8.45(dd, J=4.4, 1.5 Hz, 2H), 8.61 (dd, J=4.9, 1.7 Hz, 1H), 8.65 (d, J=1.5Hz, 2H), 10.91 (s, 1H)

N-(3-Ethylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-130)

¹H-NMR (400 MHz, DMSO-d₆)

δ 1.18 (t, J=7.6 Hz, 3H), 2.59 (q, J=7.6 Hz, 2H), 4.42 (s, 2H), 6.97 (m,1H), 7.25 (t, J=7.6 Hz, 1H), 7.28 (dd, J=7.6, 4.9 Hz, 1H), 7.41 (dd,J=4.9, 1.5 Hz, 2H), 7.49 (d, J=7.9 Hz, 1H), 7.58 (s, 1H), 7.95 (dd,J=7.6, 1.5 Hz, 1H), 8.46 (dd, J=4.6, 1.2 Hz, 2H), 8.58 (dd, J=4.9, 1.5Hz, 1H), 10.40 (s, 1H)

3-Chloro-N-(4-chlorophenyl)-2-(4-pyridylmethylthio)benzamide (CompoundNo. 1-131)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.60 (s, 2H), 7.27 (dd, J=4.4, 1.7 Hz, 2H), 7.39 (dd, J=6.8, 1.9 Hz,2H), 7.49-7.53 (m, 2H), 7.64 (dd, J=6.8, 1.9 Hz, 2H), 7.74 (dd, J=6.6,2.9 Hz, 1H), 8.43 (dd, J=4.4, 1.7 Hz, 2H), 10.44 (s, 1H)

2-(4-Pyridylmethylthio)-N-(2-quinolyl)pyridine-3-carboxamide (CompoundNo. 1-132)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.28 (dd, J=7.6, 4.9 Hz, 1H), 7.41 (dd, J=4.6, 1.5 Hz,2H), 7.53 (td, J=7.0, 1.1 Hz, 1H), 7.73 (td, J=7.0, 1.1 Hz, 1H), 7.83(d, J=8.6 Hz, 1H), 7.96 (d, J=8.6 Hz, 1H), 8.08 (dd, J=7.6, 1.5 Hz, 1H),8.29 (d, J=9.0 Hz, 1H), 8.42 (d, J=9.0 Hz, 1H), 8.45 (dd, J=4.6, 1.5 Hz,2H), 8.60 (dd, J=4.9, 1.5 Hz, 1H), 11.37 (s, 1H)

2-(4-Pyridylmethylthio)-N-(5-quinolyl)pyridine-3-carboxamide (CompoundNo. 1-133)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.46 (s, 2H), 7.35 (t, J=6.5 Hz, 1H), 7.43 (d, J=5.4 Hz, 2H), 7.57(dd, J=8.6, 4.3 Hz, 1H), 7.79 (m, 2H), 7.95 (d, J=8.3 Hz, 1H), 8.18 (d,J=6.5 Hz, 1H), 8.47 (d, J=5.4 Hz, 2H), 8.51 (d, J=8.3 Hz, 1H), 8.63 (d,J=4.0 Hz, 1H), 8.94 (d, J=2.7 Hz, 1H), 10.69 (s, 1H)

N-(2-Methylquinoline-6-yl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-134)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.64 (s, 3H), 4.44 (s, 2H), 7.32 (dd, J=7.3, 4.9 Hz, 1H), 7.40 (m,3H), 7.84 (m, 1H), 7.90 (d, J=9.1 Hz, 1H), 8.03 (dd, J=7.6, 1.5 Hz, 1H),8.22 (d, J=8.6 Hz, 1H), 8.45 (m, 3H), 8.62 (dd, J=4.9, 1.5 Hz, 1H),10.75 (s, 1H)

2-(4-Pyridylmethylthio)-N-(8-quinolyl)pyridine-3-carboxamide (CompoundNo. 1-135)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.46 (s, 2H), 7.36 (dd, J=7.7, 4.9 Hz, 1H), 7.43 (dd, J=4.6, 1.5 Hz,2H), 7.67-7.68 (m, 2H), 7.78 (dd, J=8.2, 1.2 Hz, 1H), 8.17 (dd, J=7.6,1.8 Hz, 1H), 8.46-8.47 (m, 2H), 8.66-8.67 (m, 2H), 8.93 (dd, J=4.6, 1.5Hz, 2H), 10.56 (s, 1H)

N-(5-Indanyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide (CompoundNo. 1-136)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.01 (t, J=7.6 Hz, 2H), 2.81-2.83 (m, 4H), 4.41 (s, 2H), 7.17 (d,J=8.0 Hz, 1H), 7.28 (dd, J=7.6, 4.8 Hz, 1H), 7.40-7.41 (m, 3H), 7.61 (s,1H), 7.93 (dd, J=7.6, 1.5 Hz, 1H), 8.45 (dd, J=4.6, 1.5 Hz, 2H), 8.58(dd, J=4.8, 1.8 Hz, 1H), 10.34 (s, 1H)

N-(3-Chloro-4-trifluoromethoxyphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-137)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.32 (dd, J=7.6, 4.8 Hz, 1H), 7.40 (d, J=4.9 Hz, 2H),7.58 (d, J=9.0 Hz, 1H), 7.71 (dd, J=9.0, 2.4 Hz, 1H), 8.01 (dd, J=7.6,1.7 Hz, 1H), 8.08 (d, J=2.4 Hz, 1H), 8.45 (dd, J=4.9, 1.5 Hz, 2H), 8.61(dd, J=4.8, 1.7 Hz, 1H), 10.82 (s, 1H)

N-(2-Methylbenzothiazol-5-yl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-138)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.80 (s, 3H), 4.43 (s, 2H), 7.31 (dd, J=7.6, 4.9 Hz, 1H), 7.41 (dd,J=4.4, 1.5 Hz, 2H), 7.67 (d, J=7.8 Hz, 1H), 7.98 (d, J=7.8 Hz, 1H), 8.02(dd, J=7.6, 1.5 Hz, 1H), 8.35 (s, 1H), 8.45 (dd, J=4.4, 1.5 Hz, 2H),8.60 (dd, J=4.9, 1.5 Hz, 1H), 10.61 (s, 1H)

N-(2-Methylindol-5-yl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-139)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.37 (s, 3H), 4.41 (s, 2H), 6.09 (s, 1H), 7.21 (s, 1H), 7.28 (dd,J=7.6, 4.9 Hz, 1H), 7.40 (d, J=4.4, 1.5 Hz, 2H), 7.81 (s, 1H), 7.94 (dd,J=7.6, 1.6 Hz, 1H), 8.45 (dd, J=4.4, 1.5 Hz, 2H), 8.57 (dd, J=4.9, 1.6Hz, 1H), 10.21 (s, 1H), 10.86 (s, 1H)

N-(3-Methylphenyl)-2-(4-pyridylmethylthio)benzamide (Compound No. 1-140)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.30 (s, 3H), 4.25 (s, 2H), 6.91 (d, J=7.6 Hz, 1H), 7.21 (t, J=7.8 Hz,1H), 7.28 (t, J=7.3 Hz, 1H), 7.36 (d, J=4.8 Hz, 2H), 7.40 (t, J=7.3 Hz,1H), 7.48-7.49 (m, 3H), 7.59 (s, 1H), 8.46 (d, J=4.8 Hz, 2H), 10.27 (s,1H)

N-(3-Ethylphenyl)-2-(4-pyridylmethylthio)benzamide (Compound No. 1-141)

¹H-NMR (400 MHz, DMSO-d₆)

δ 1.18 (t, J=7.6 Hz, 3H), 2.58 (q, J=7.6 Hz, 2H), 4.26 (s, 2H), 6.94 (d,J=7.6 Hz, 1H), 7.24 (t, J=7.6 Hz, 1H), 7.28 (td, J=7.3, 1.2 Hz, 1H),7.36 (dd, J=4.6, 1.5 Hz, 2H), 7.41 (dd, J=7.3, 1.5 Hz, 1H), 7.46 (m,1H), 7.51 (m, 2H), 7.62 (s, 1H), 8.46 (dd, J=4.6, 1.5 Hz, 2H), 10.29 (s,1H)

N-(3-Fluoro-4-methylphenyl)-2-(4-pyridylmethylthio)benzamide (CompoundNo. 1-142)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.20 (s, 3H), 4.26 (s, 2H), 7.23 (t, J=8.6 Hz, 1H), 7.29 (t, J=7.3 Hz,1H), 7.35 (dd, J=4.3, 1.5 Hz, 2H), 7.37 (m, 1H), 7.41 (m, 1H), 7.46 (m,1H), 7.51 (d, J=7.6 Hz, 1H), 7.63 (d, J=11.9 Hz, 1H), 8.46 (dd, J=4.3,1.5 Hz, 2H), 10.46 (s, 1H)

N-(4-Fluoro-3-methylphenyl)-2-(4-pyridylmethylthio)benzamide (CompoundNo. 1-143)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.23 (d, J=1.4 Hz, 3H), 4.25 (s, 2H), 7.11 (t, J=9.3 Hz, 1H), 7.28(td, J=7.5, 1.2 Hz, 1H), 7.36 (dd, J=4.4, 1.5 Hz, 2H), 7.41 (td, J=8.7,1.5 Hz, 1H), 7.46 (dd, J=8.1, 1.0 Hz, 1H), 7.50-7.51 (m, 2H), 7.66 (m,1H), 8.46 (dd, J=4.4, 1.5 Hz, 2H), 10.34 (s, 1H)

N-(5-Benzotriazolyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-144)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.31 (dd, J=7.7, 4.9 Hz, 1H), 7.40 (dd, J=4.5, 1.7 Hz,2H), 7.52 (d, J=8.9 Hz, 1H), 7.93 (d, J=8.5 Hz, 1H), 8.01 (dd, J=7.7,1.5 Hz, 1H), 8.41 (s, 1H), 8.44 (dd, J=4.5, 1.7 Hz, 2H), 8.60 (dd,J=4.9, 1.5 Hz, 1H), 10.73 (s, 1H), 15.58 (s, 1H)

N-(5-Indolyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide (CompoundNo. 1-145)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.42 (s, 2H), 6.41 (s, 1H), 7.29 (m, 1H), 7.32-7.35 (m, 3H), 7.41 (d,J=6.1 Hz, 2H), 7.95-7.97 (m, 2H), 8.45 (dd, J=4.5, 1.5 Hz, 2H), 8.57(dd, J=4.9, 1.6 Hz, 1H), 10.27 (s, 1H), 11.04 (s, 1H)

N-(3,5-Dimethoxyphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-146)

¹H-NMR (500 MHz, DMSO-d₆)

δ 3.72 (s, 6H), 4.42 (s, 2H), 6.28 (t, J=2.3 Hz, 1H), 6.96 (s, 2H), 7.29(dd, J=7.6, 4.9 Hz, 1H), 7.40 (dd, J=4.6, 1.6 Hz, 2H), 7.93 (d, J=7.6,1.5 Hz, 1H), 8.45 (dd, J=4.6, 1.6 Hz, 2H), 8.58 (dd, J=4.9, 1.5 Hz, 1H),10.39 (s, 1H)

2-(4-Pyridylmethylthio)-N-(4-vinylphenyl)pyridine-3-carboxamide(Compound No. 1-147)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.42 (s, 2H), 5.20 (dd, J=10.9, 1.0 Hz, 1H), 5.77 (dd, J=17.7, 1.0 Hz,1H), 6.69 (dd, J=17.7, 10.9 Hz, 1H), 7.29 (dd, J=7.6, 4.9 Hz, 1H), 7.40(dd, J=4.4, 1.5 Hz, 2H), 7.46 (d, J=8.8 Hz, 2H), 7.68 (d, J=8.8 Hz, 2H),7.97 (dd, J=7.6, 1.6 Hz, 1H), 8.45 (dd, J=4.4, 1.5 Hz, 2H), 8.59 (dd,J=4.9, 1.6 Hz, 1H), 10.53 (s, 1H)

N-(3-Methanesulfonylaminophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-148)

¹H-NMR (400 MHz, DMSO-d₆)

δ 3.00 (s, 3H), 4.42 (s, 2H), 6.95 (ddd, J=8.1, 2.0, 0.8 Hz, 1H),7.27-7.31 (m, 2H), 7.40 (dd, J=4.4, 1.6 Hz, 2H), 7.44 (d, J=8.1 Hz, 1H),7.66 (d, J=2.0 Hz, 1H), 7.96 (dd, J=7.6, 1.7 Hz, 1H), 8.45 (dd, J=4.4,1.6 Hz, 2H), 8.58 (dd, J=4.7, 1.7 Hz, 1H), 9.80 (s, 1H), 10.54 (s, 1H)

N-(1-Acetyl-2,3-dihydroindol-5-yl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-149)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.14 (s, 3H), 3.15 (t, J=8.3 Hz, 2H), 4.09 (t, J=8.3 Hz, 2H), 4.41 (s,2H), 7.28 (dd, J=7.6, 4.9 Hz, 1H), 7.37 (m, 1H), 7.40 (dd, J=4.4, 1.7Hz, 2H), 7.65 (s, 1H), 7.94 (d, J=7.6 Hz, 1H), 7.98 (d, J=8.6 Hz, 1H),8.45 (dd, J=4.4, 1.7 Hz, 2H), 8.58 (dd, J=4.9, 1.8 Hz, 1H), 10.39 (s,1H)

N-(6-Indolyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide (CompoundNo. 1-150)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.21 (s, 2H), 6.38 (s, 1H), 7.16 (d, J=8.5 Hz, 1H), 7.27-7.30 (m, 2H),7.41 (d, J=5.7 Hz, 2H), 7.47 (d, J=8.3 Hz, 1H), 7.96 (d, J=6.4 Hz, 1H),8.05 (s, 1H), 8.45 (d, J=5.7 Hz, 2H), 8.58 (d, J=3.2 Hz, 1H), 10.37 (s,1H), 11.06 (s, 1H)

N-(4 Cyanomethylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-151)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.00 (s, 2H), 4.41 (s, 2H), 7.29 (dd, J=7.6, 4.9 Hz, 1H), 7.32 (d,J=8.6 Hz, 2H), 7.40 (dd, J=4.5, 1.6 Hz, 2H), 7.70 (dd, J=8.6 Hz, 2H),7.98 (dd, J=7.6, 1.5 Hz, 1H), 8.45 (dd, J=4.5, 1.6 Hz, 2H), 8.58 (dd,J=4.9, 1.5 Hz, 1H), 10.55 (s, 1H)

N-(5-Methyl-3-trifluoromethylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-152)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.39 (s, 3H), 4.42 (s, 2H), 7.31 (dd, J=7.6, 4.9 Hz, 1H), 7.32 (m,1H), 7.41 (dd, J=4.4, 1.7 Hz, 2H), 7.76 (s, 1H), 7.95 (s, 1H), 8.02 (dd,J=7.6, 1.7 Hz, 1H), 8.46 (dd, J=4.4, 1.7 Hz, 2H), 8.61 (dd, J=4.9, 1.7Hz, 1H), 10.72 (s, 1H)

N-(4-Nitro-3-trifluoromethylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-153)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.44 (s, 2H), 7.35 (dd, J=7.6, 4.9 Hz, 1H), 7.41 (dd, J=4.4, 1.5 Hz,2H), 8.10 (dd, J=7.6, 1.8 Hz, 1H), 8.19 (dd, J=9.0, 2.2 Hz, 1H), 8.27(d, J=9.0 Hz, 1H), 8.37 (d, J=2.2 Hz, 1H), 8.45 (dd, J=4.4, 1.5 Hz, 2H),8.65 (dd, J=4.9, 1.8 Hz, 1H), 11.23 (s, 1H)

N-(3-Chloro-4-cyanophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-154)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.34 (dd, J=7.6, 4.9 Hz, 1H), 7.40 (dd, J=4.4, 1.7 Hz,2H), 7.76 (dd, J=8.7, 2.0 Hz, 1H), 7.96 (d, J=8.7 Hz, 1H), 8.04 (dd,J=7.6, 1.6 Hz, 1H), 8.13 (d, J=2.0 Hz, 1H), 8.48 (dd, J=4.4, 1.7 Hz,2H), 8.63 (dd, J=4.9, 1.6 Hz, 1H), 11.05 (s, 1H)

N-(5-Indazolyl)-2-(4-pyridylmethylthio)benzamide (Compound No. 1-155)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.26 (s, 2H), 7.27-7.56 (m, 8H), 8.06 (s, 1H), 8.26 (s, 1H), 8.46 (dd,J=4.4, 1.5 Hz, 2H), 10.36 (s, 1H), 13.01 (s, 1H)

N-(6-Indazolyl)-2-(4-pyridylmethylthio)benzamide (Compound No. 1-156)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.27 (s, 2H), 7.26 (d, J=8.6 Hz, 1H), 7.31 (t, J=7.6 Hz, 1H), 7.36 (d,J=5.8 Hz, 2H), 7.42 (t, J=8.6 Hz, 1H), 7.48 (d, J=7.6 Hz, 1H), 7.54 (d,J=6.7 Hz, 1H), 7.68 (d, J=8.6 Hz, 1H), 7.99 (s, 1H), 8.25 (s, 1H), 8.45(d, J=5.8 Hz, 2H), 10.50 (s, 1H), 12.93 (s, 1H)

N-(4-Cyano-3-trifluoromethylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-157)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.35 (dd, J=7.6, 4.9 Hz, 1H), 7.40 (dd, J=4.6, 1.8 Hz,2H), 8.08 (dd, J=7.6, 1.5 Hz, 1H), 8.11-8.17 (m, 2H), 8.36 (d, J=1.8 Hz,1H), 8.46 (dd, J=4.6, 1.8 Hz, 2H), 8.64 (dd, J=4.9, 1.5 Hz, 1H), 11.19(s, 1H)

2-(4-Pyridylmethylthio)-N-(4-trifluoromethylthiophenyl)pyridine-3-carboxamide(Compound No. 1-158)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.31 (dd, J=7.6, 4.8 Hz, 1H), 7.40 (dd, J=4.6, 1.8 Hz,2H), 7.71 (d, J=6.8 Hz, 2H), 7.86 (dd, J=6.8, 2.2 Hz, 2H), 8.00 (dd,J=7.6, 1.8 Hz, 1H), 8.45 (dd, J=4.6, 1.8 Hz, 2H), 8.61 (dd, J=4.8, 1.8Hz, 1H), 10.79 (s, 1H)

N-(3-Chloro-4-trifluoromethylthiophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-159)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.33 (dd, J=7.8, 4.9 Hz, 1H), 7.40 (dd, J=4.4, 1.5 Hz,2H), 7.76 (dd, J=8.6, 2.2 Hz, 1H), 7.89 (d, J=8.6 Hz, 1H), 8.03 (dd,J=7.8, 1.7 Hz, 1H), 8.15 (d, J=2.2 Hz, 1H), 8.45 (dd, J=4.4, 1.5 Hz,2H), 8.62 (dd, J=4.9, 1.7 Hz, 1H), 10.93 (s, 1H)

N-(5-Indanyl)-2-(4-pyridylmethylthio)benzamide (Compound No. 1-160)

¹H-NMR (500 MHz, DMSO-d₆)

δ 1.98-2.04 (m, 2H), 2.69-2.86 (m, 4H), 4.24 (s, 2H), 7.16 (d, J=7.9 Hz,1H), 7.28 (t, J=7.6 Hz, 1H), 7.35 (dd, J=4.5, 1.5 Hz, 2H), 7.38-7.46 (m,3H), 7.49 (d, J=7.3 Hz, 1H), 7.66 (s, 1H), 8.45 (dd, J=4.5, 1.5 Hz, 2H),10.23 (s, 1H)

N-(6-Benzothiazolyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-161)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.32 (dd, J=7.6, 4.9 Hz, 1H), 7.41 (dd, J=4.4, 1.6 Hz,2H), 7.71 (dd, J=8.5, 1.5 Hz, 1H), 8.02 (dd, J=7.6, 1.8 Hz, 1H), 8.06(d, J=8.5 Hz, 1H), 8.45 (dd, J=4.4, 1.6 Hz, 2H), 8.61 (dd, J=4.9, 1.8Hz, 1H), 8.64 (d, J=1.5 Hz, 1H), 9.31 (s, 1H), 10.74 (s, 1H)

N-(2-Methylthiobenzothiazol-6-0-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-162)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.79 (s, 3H), 4.43 (s, 2H), 7.31 (dd, J=7.6, 4.9 Hz, 1H), 7.40 (dd,J=4.5, 1.5 Hz, 2H), 7.62 (dd, J=8.8, 1.5 Hz, 1H), 7.82 (d, J=8.8 Hz,1H), 8.00 (dd, J=7.6, 1.8 Hz, 1H), 8.45 (dd, J=4.5, 1.5 Hz, 2H), 8.49(d, J=1.5 Hz, 1H), 8.60 (dd, J=4.9, 1.8 Hz, 1H), 10.69 (s, 1H)

N-(Coumarin-6-O-2-(4-pyridylmethylthio)pyridine-3-carboxamide (CompoundNo. 1-163)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 6.51 (d, J=9.8 Hz, 1H), 7.31 (dd, J=7.6, 4.9 Hz, 1H),7.40 (dd, J=4.4, 1.5 Hz, 2H), 7.42 (d, J=9.8 Hz, 1H), 7.75 (dd, J=9.0,2.2 Hz, 1H), 8.01 (dd, J=7.6, 1.8 Hz, 1H), 8.13 (d, J=9.0 Hz, 1H), 8.19(d, J=2.2 Hz, 1H), 8.46 (dd, J=4.4, 1.6 Hz, 2H), 8.61 (dd, J=4.9, 1.8Hz, 1H), 10.70 (s, 1H)

N-(6-Phthalidyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide (CompoundNo. 1-164)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.40 (s, 2H), 5.38 (s, 2H), 7.29 (dd, J=7.6, 4.7 Hz, 1H), 7.40 (dd,J=4.3, 1.5 Hz, 2H), 7.62 (d, J=7.9 Hz, 1H), 7.92 (dd, J=7.9, 1.2 Hz,1H), 8.05 (dd, J=7.6, 1.8 Hz, 1H), 8.27 (d, J=1.6 Hz, 1H), 8.45 (dd,J=4.3, 1.5 Hz, 2H), 8.58 (dd, J=4.7, 1.8 Hz, 1H), 10.82 (s, 1H)

2-(4-Pyridylmethylthio)-N-(6-quionolyl)benzamide (Compound No. 1-165)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.28 (s, 2H), 7.32 (m, 1H), 7.36-7.37 (m, 2H), 7.45 (m, 1H), 7.49-7.52(m, 2H), 7.59-7.61 (m, 1H), 7.91 (d, J=9.0 Hz, 1H), 8.00 (d, J=9.0 Hz,1H), 8.34 (d, J=9.0 Hz, 1H), 8.46 (dd, J=4.4, 1.7 Hz, 2H), 8.56 (s, 1H),8.81 (dd, J=4.2, 1.7 Hz, 1H), 10.72 (s, 1H)

N-(2,2-Difluoro-1,3-benzodioxol-5-yl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-166)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.42 (s, 2H), 7.31 (dd, J=7.6, 4.9 Hz, 1H), 7.39-7.40 (m, 4H), 7.83(s, 1H), 7.98 (dd, J=7.6, 1.8 Hz, 1H), 8.46 (dd, J=4.5, 1.8 Hz, 2H),8.80 (dd, J=4.9, 1.8 Hz, 1H), 10.68 (s, 1H)

2-(4-Pyridylmethylthio)-N-(2,2,3,3-tetrafluoro-1,4-benzodioxane-6-O-pyridine-3-carboxamide(Compound No. 1-167)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.31 (dd, J=7.6, 4.9 Hz, 1H), 7.40 (dd, J=4.3, 1.5 Hz,2H), 7.49 (d, J=8.9 Hz, 1H), 7.54 (dd, J=8.9, 2.1 Hz, 1H), 7.87 (d,J=2.1 Hz, 1H), 7.99 (dd, J=7.6, 1.8 Hz, 1H), 8.46 (dd, J=4.3, 1.5 Hz,2H), 8.61 (dd, J=4.9, 1.8 Hz, 1H), 10.78 (s, 1H)

N-(1,3-Benzodioxol-5-yl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-168)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.41 (s, 2H), 6.00 (s, 2H), 6.89 (d, J=8.6 Hz, 1H), 7.10 (dd, J=8.6,1.3 Hz, 1H), 7.28 (dd, J=7.6, 4.9 Hz, 1H), 7.36 (s, 1H), 7.40 (dd,J=4.3, 1.5 Hz, 2H), 7.93 (dd, J=7.6, 1.5 Hz, 1H), 8.46 (dd, J=4.3, 1.5Hz, 2H), 8.58 (dd, J=4.9, 1.8 Hz, 1H), 10.36 (s, 1H)

N-(1-Acetyl-2,3-dihydroindol-6-yl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-169)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.16 (s, 3H), 3.10 (t, J=8.3 Hz, 2H), 4.10 (t, J=8.3 Hz, 2H), 4.41 (s,2H), 7.17 (d, J=6.1 Hz, 1H), 7.26 (dd, J=7.6, 4.9 Hz, 1H), 7.40 (d,J=6.1 Hz, 2H), 7.47 (m, 1H), 7.95 (dd, J=7.6, 1.5 Hz, 1H), 8.33 (s, 1H),8.45 (d, J=6.1 Hz, 2H), 8.56 (dd, J=4.9, 1.6 Hz, 1H), 10.43 (s, 1H)

N-(1-Oxoindane-5-yl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-170)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.58-2.63 (m, 2H), 3.10 (t, J=5.3 Hz, 2H), 4.43 (s, 2H), 7.31 (dd,J=7.5, 4.9 Hz, 1H), 7.40 (dd, J=4.4, 1.7 Hz, 2H), 7.63 (s, 2H), 8.00(dd, J=7.5, 1.7 Hz, 1H), 8.03 (s, 1H), 8.45 (dd, J=4.4, 1.7 Hz, 2H),8.61 (dd, J=4.9, 1.7 Hz, 1H), 10.83 (s, 1H)

N-(4-n-Propoxyphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-171)

¹H-NMR (500 MHz, DMSO-d₆)

δ 0.97 (t, J=7.5 Hz, 3H), 1.70-1.74 (m, 2H), 3.90 (t, J=7.5 Hz, 2H),4.41 (s, 2H), 6.91 (d, J=9.2 Hz, 2H), 7.27 (dd, J=7.5, 4.6 Hz, 1H), 7.40(dd, J=4.5, 1.5 Hz, 2H), 7.59 (d, J=9.2 Hz, 2H), 7.94 (dd, J=7.5, 1.8Hz, 1H), 8.45 (dd, J=4.5, 1.5 Hz, 2H), 8.57 (dd, J=4.6, 1.8 Hz, 1H),10.31 (s, 1H)

N-(4-Isopropylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-172)

¹H-NMR (500 MHz, DMSO-d₆)

δ 1.19 (d, J=6.7 Hz, 6H), 2.86 (m, 1H), 4.42 (s, 2H), 7.21 (d, J=8.6 Hz,2H), 7.28 (dd, J=7.6, 4.9 Hz, 1H), 7.40 (dd, J=4.6, 1.6 Hz, 2H), 7.60(d, J=8.6 Hz, 2H), 7.94 (dd, J=7.6, 1.8 Hz, 1H), 8.45 (dd, J=4.6, 1.6Hz, 2H), 8.59 (dd, J=4.9, 1.8 Hz, 1H), 10.39 (s, 1H)

N-(4-Ethylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-173)

¹H-NMR (500 MHz, DMSO-d₆)

δ 1.17 (t, J=7.5 Hz, 3H), 2.57 (q, J=7.5 Hz, 2H), 4.41 (s, 2H), 7.18 (d,J=8.5 Hz, 2H), 7.28 (dd, J=7.6, 4.9 Hz, 1H), 7.40 (dd, J=4.3, 1.5 Hz,2H), 7.59 (d, J=8.5 Hz, 2H), 7.94 (dd, J=7.6, 1.6 Hz, 1H), 8.45 (dd,J=4.3, 1.5 Hz, 2H), 8.58 (dd, J=4.9, 1.6 Hz, 1H), 10.38 (s, 1H)

N-(4-Methylthiophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-174)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.46 (s, 3H), 4.42 (s, 2H), 7.25-7.30 (m, 3H), 7.40 (dd, J=4.4, 1.5Hz, 2H), 7.65 (d, J=8.5 Hz, 2H), 7.95 (dd, J=7.6, 1.5 Hz, 1H), 8.45 (dd,J=4.4, 1.5 Hz, 2H), 8.58 (dd, J=4.9, 1.5 Hz, 1H), 10.47 (s, 1H)

N-(3-Methyl-4-trifluoromethoxyphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-175)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.27 (s, 3H), 4.42 (s, 2H), 7.28-7.32 (m, 2H), 7.40 (dd, J=4.4, 1.7Hz, 2H), 7.59 (dd, J=8.7, 2.2 Hz, 1H), 7.72 (d, J=2.2 Hz, 1H), 7.96 (dd,J=7.6, 1.7 Hz, 1H), 8.45 (dd, J=4.4, 1.7 Hz, 2H), 8.60 (dd, J=4.9, 1.7Hz, 1H), 10.58 (s, 1H)

N-(4-n-Butyrylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-176)

¹H-NMR (500 MHz, DMSO-d₆)

δ 0.93 (t, J=7.3 Hz, 3H), 1.61-1.66 (m, 2H), 2.96 (t, J=7.1 Hz, 2H),4.43 (s, 2H), 7.31 (dd, J=7.6, 4.9 Hz, 1H), 7.41 (dd, J=4.6, 1.6 Hz,2H), 7.83 (d, J=8.6 Hz, 2H), 7.98 (dd, J=8.6, 1.8 Hz, 2H), 8.01 (dd,J=7.6, 1.6 Hz, 1H), 8.45 (dd, J=4.6, 1.6 Hz, 2H), 8.61 (dd, J=4.9, 1.6Hz, 1H), 10.77 (s, 1H)

N-(1-Oxo-1,2,3,4-tetrahydronaphthalene-6-yl)-2-(4-pyridylmethylthio)-pyridine-3-carboxamide(Compound No. 1-177)

¹H-NMR (500 MHz, CDCl₃)

δ 2.13-2.17 (m, 2H), 2.65 (t, J=6.7 Hz, 2H), 2.98 (t, J=6.1 Hz, 2H),4.48 (s, 2H), 7.17 (dd, J=7.6, 4.9 Hz, 1H), 7.39 (dd, J=8.6, 1.8 Hz,1H), 7.35 (dd, J=4.5, 1.5 Hz, 2H), 7.81 (d, J=1.8 Hz, 1H), 7.92 (dd,J=7.6, 1.6 Hz, 1H), 8.01 (s, 1H), 8.04 (d, J=8.6 Hz, 1H), 8.50 (dd,J=4.5, 1.5 Hz, 2H), 8.57 (dd, J=4.9, 1.6 Hz, 1H)

N-(4-Cyclohexylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-178)

¹H-NMR (500 MHz, DMSO-d₆)

δ 1.16-1.27 (m, 1H), 1.31-1.43 (m, 4H), 1.69 (d, J=6.5 Hz, 1H),1.73-1.81 (m, 4H), 2.45 (m, 1H), 4.41 (s, 2H), 7.19 (d, J=8.6 Hz, 2H),7.28 (dd, J=7.6, 4.9 Hz, 1H), 7.40 (dd, J=4.6, 1.5 Hz, 2H), 7.58 (d,J=8.6 Hz, 2H), 7.93 (dd, J=7.6, 1.5 Hz, 1H), 8.45 (dd, J=4.6, 1.5 Hz,2H), 8.58 (dd, J=4.9, 1.5 Hz, 1H), 10.37 (s, 1H)

2-(4-Pyridylmethylthio)-N-(3-trifluoromethylthiophenyl)pyridine-3-carboxamide(Compound No. 1-179)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.31 (dd, J=7.6, 4.8 Hz, 1H), 7.40 (dd, J=4.4, 1.7 Hz,2H), 7.46 (d, J=8.1 Hz, 1H), 7.54 (t, J=8.1 Hz, 1H), 7.86 (d, J=8.1 Hz,1H), 8.02 (dd, J=7.6, 1.7 Hz, 1H), 8.16 (s, 1H), 8.45 (dd, J=4.4, 1.7Hz, 2H), 8.60 (dd, J=4.8, 1.7 Hz, 1H), 10.74 (s, 1H)

N-(3,5-Dimethyl-4-trifluoromethoxyphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-180)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.26 (s, 6H), 4.42 (s, 2H), 7.29 (dd, J=7.6, 4.9 Hz, 1H), 7.40 (dd,J=4.5, 1.8 Hz, 2H), 7.52 (s, 2H), 7.95 (dd, J=7.6, 1.5 Hz, 1H), 8.45(dd, J=4.5, 1.8 Hz, 2H), 8.59 (dd, J=4.9, 1.5 Hz, 1H), 10.51 (s, 1H)

N-(3-Nitrophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-181)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.33 (dd, J=7.8, 4.7 Hz, 1H), 7.41 (dd, J=4.4, 1.5 Hz,2H), 7.67 (m, 1H), 7.98-8.05 (m, 3H), 8.46 (dd, J=4.4, 1.5 Hz, 2H), 8.63(dd, J=4.7, 1.8 Hz, 1H), 8.74 (m, 1H), 10.90 (s, 1H)

N-(3-Cyano-4-methylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-182)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.45 (s, 3H), 4.42 (s, 2H), 7.31 (dd, J=7.5, 4.7 Hz, 1H), 7.40 (dd,J=4.4, 1.5 Hz, 2H), 7.46 (d, J=8.5 Hz, 1H), 7.82 (dd, J=8.5, 2.2 Hz,1H), 8.00 (dd, J=7.5, 1.7 Hz, 1H), 8.10 (d, J=2.2 Hz, 1H), 8.46 (dd,J=4.4, 1.5 Hz, 2H), 8.61 (dd, J=4.7, 1.7 Hz, 1H), 10.70 (s, 1H)

N-(3-Cyanophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-183)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.32 (dd, J=7.6, 4.8 Hz, 1H), 7.40 (dd, J=4.4, 1.7 Hz,2H), 7.56-7.61 (m, 2H), 7.94 (m, 1H), 8.02 (dd, J=7.6, 1.7 Hz, 1H), 8.17(d, J=1.0 Hz, 1H), 8.46 (dd, J=4.4, 1.7 Hz, 2H), 8.62 (dd, J=4.8, 1.7Hz, 1H), 10.80 (s, 1H)

N-(3-Chloro-4-methoxyphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-184)

¹H-NMR (400 MHz, DMSO-d₆)

δ 3.84 (s, 3H), 4.42 (s, 2H), 7.15 (d, J=8.8 Hz, 1H), 7.29 (d, J=7.6,4.9 Hz, 1H), 7.40 (d, J=6.1 Hz, 2H), 7.56 (dd, J=8.8, 2.4 Hz, 1H), 7.86(d, J=2.4 Hz, 1H), 7.97 (dd, J=7.6, 1.7 Hz, 1H), 8.45 (d, J=6.1 Hz, 2H),8.59 (dd, J=4.9, 1.7 Hz, 1H), 10.47 (s, 1H)

N-(4-Fluoro-3-nitrophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-185)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.33 (dd, J=7.6, 4.7 Hz, 1H), 7.41 (d, J=5.8 Hz, 2H),7.62 (m, 1H), 8.00 (m, 1H), 8.04 (dd, J=7.6, 1.5 Hz, 1H), 8.46 (d, J=5.8Hz, 2H), 8.62-8.64 (m, 2H), 10.92 (s, 1H)

N-(3-Aminophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-186)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.41 (s, 2H), 5.11 (s, 2H), 6.31 (ddd, J=8.0, 2.2, 1.0 Hz, 1H), 6.76(d, J=8.0 Hz, 1H), 6.95 (m, 1H), 7.05 (s, 1H), 7.28 (m, 1H), 7.40 (dd,J=4.4, 1.7 Hz, 2H), 7.89 (dd, J=7.6, 1.7 Hz, 1H), 8.45 (dd, J=4.4, 1.7Hz, 2H), 8.56 (dd, J=4.9, 1.7 Hz, 1H), 10.20 (s, 1H)

N-(3-Bromo-4-trifluoromethoxyphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-187)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.32 (m, 1H), 7.40 (dd, J=Hz, 2H), 7.56 (dd, J=9.1, 1.2Hz, 1H), 7.75 (dd, J=9.1, 1.2 Hz, 1H), 8.01 (dd, J=7.6, 1.8 Hz, 1H),8.22 (d, J=2.4 Hz, 1H), 8.45 (dd, J=4.4, 1.7 Hz, 2H), 8.62 (dd, J=4.9,1.8 Hz, 1H), 10.79 (s, 1H)

N-(3-Fluoro-4-methoxyphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-188)

¹H-NMR (400 MHz, DMSO-d₆)

δ 3.82 (s, 3H), 4.42 (s, 2H), 7.16 (m, 1H), 7.29 (dd, J=7.6, 4.9 Hz,1H), 7.38-7.41 (m, 3H), 7.65 (dd, J=13.6, 2.4 Hz, 1H), 7.96 (dd, J=7.6,1.7 Hz, 1H), 8.45 (dd, J=4.4, 1.5 Hz, 2H), 8.59 (dd, J=4.9, 1.7 Hz, 1H),10.49 (s, 1H)

N-(4-Difluoromethoxyphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-189)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.42 (s, 2H), 7.18-7.20 (m, 3H), 7.30 (dd, J=7.6, 4.9 Hz, 1H), 7.40(dd, J=4.6, 1.7 Hz, 2H), 7.73 (d, J=9.0 Hz, 2H), 7.97 (dd, J=7.6, 1.7Hz, 1H), 8.46 (dd, J=4.6, 1.7 Hz, 2H), 8.59 (dd, J=4.9, 1.7 Hz, 1H),10.56 (s, 1H)

N-(3-Ethoxyphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-190)

¹H-NMR (500 MHz, DMSO-d₆)

δ 1.33 (t, J=7.0 Hz, 3H), 4.00 (q, J=7.0 Hz, 2H), 4.42 (s, 2H), 6.68 (m,1H), 7.22-7.24 (m, 2H), 7.29 (dd, J=7.6, 4.9 Hz, 1H), 7.37 (s, 1H), 7.40(dd, J=4.6, 1.8 Hz, 2H), 7.95 (dd, J=7.6, 1.5 Hz, 1H), 8.45 (dd, J=4.6,1.8 Hz, 2H), 8.59 (dd, J=4.9, 1.5 Hz, 1H), 10.42 (s, 1H)

N-(4-sec-Butylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-191)

¹H-NMR (500 MHz, DMSO-d₆)

δ 0.76 (t, J=7.3 Hz, 3H), 1.17 (d, J=7.0 Hz, 3H), 1.50-1.57 (m, 2H),2.56 (m, 1H), 4.41 (s, 2H), 7.17 (d, J=8.4 Hz, 2H), 7.28 (dd, J=7.6, 4.7Hz, 1H), 7.40 (dd, J=4.4, 1.6 Hz, 2H), 7.60 (d, J=8.4 Hz, 2H), 7.94 (dd,J=7.6, 1.8 Hz, 1H), 8.45 (dd, J=4.4, 1.6 Hz, 2H), 8.58 (dd, J=4.7, 1.8Hz, 1H), 10.38 (s, 1H)

N-(3,5-Difluorophenyl)-2 (4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-192)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.00 (m, 1H), 7.32 (dd, J=7.6, 4.9 Hz, 1H), 7.40 (dd,J=4.6, 1.5 Hz, 2H), 7.43 (dd, J=9.5, 1.8 Hz, 2H), 8.00 (dd, J=7.6, 1.7Hz, 1H), 8.45 (dd, J=4.6, 1.5 Hz, 2H), 8.61 (dd, J=4.9, 1.7 Hz, 1H),10.82 (s, 1H)

2-(4° Pyridylmethylthio)-N-(3,4,5-trichlorophenyl)pyridine-3-carboxamide(Compound No. 1-193)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.33 (dd, J=7.6, 4.9 Hz, 1H), 7.40 (dd, J=4.4, 1.6 Hz,2H), 7.98 (s, 2H), 8.03 (dd, J=7.6, 1.8 Hz, 1H), 8.46 (dd, J=4.4, 1.6Hz, 2H), 8.62 (dd, J=4.9, 1.8 Hz, 1H), 10.84 (s, 1H)

N-(3-Methylthiophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-194)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.47 (s, 3H), 4.42 (s, 2H), 7.01 (d, J=7.9 Hz, 1H), 7.27-7.31 (m, 2H),7.40 (dd, J=4.5, 1.6 Hz, 2H), 7.46 (d, J=7.9 Hz, 1H), 7.67 (s, 1H), 7.97(dd, J=7.6, 1.5 Hz, 1H), 8.45 (dd, J=4.5, 1.6 Hz, 2H), 8.59 (dd, J=4.9,1.5 Hz, 1H), 10.48 (s, 1H)

N-(4-Chloro-3-nitrophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-195)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.33 (dd, J=7.6, 4.9 Hz, 1H), 7.40 (dd, J=4.4, 1.7 Hz,2H), 7.78 (d, J=8.9 Hz, 1H), 7.92 (d, J=8.9 Hz, 1H), 8.05 (dd, J=7.6,1.8 Hz, 1H), 8.45 (dd, J=4.4, 1.7 Hz, 2H), 8.52 (d, J=2.7 Hz, 1H), 8.63(dd, J=4.9, 1.8 Hz, 1H), 11.00 (s, 1H)

N-(3,4-Dicyanophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-196)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.34 (dd, J=7.6, 4.9 Hz, 1H), 7.40 (dd, J=4.3, 1.5 Hz,2H), 8.05-8.13 (m, 3H), 8.36 (d, J=1.5 Hz, 1H), 8.45 (dd, J=4.3, 1.5 Hz,2H), 8.64 (dd, J=4.9, 1.5 Hz, 1H), 11.19 (s, 1H)

N-(4-Diethylaminophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-197)

¹H-NMR (500 MHz, DMSO-d₆)

δ 1.07 (t, J=7.0 Hz, 6H), 3.29-3.33 (m, 4H), 4.40 (s, 2H), 6.64 (d,J=9.2 Hz, 2H), 7.26 (dd, J=7.6, 4.9 Hz, 1H), 7.40 (dd, J=4.3, 1.5 Hz,2H), 7.46 (d, J=9.2 Hz, 2H), 7.90 (dd, J=7.6, 1.8 Hz, 1H), 8.45 (dd,J=4.3, 1.5 Hz, 2H), 8.55 (dd, J=4.9, 1.8 Hz, 1H), 10.11 (s, 1H)

N-(3-Benzyloxyphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-198)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.42 (s, 2H), 5.09 (s, 2H), 6.78 (m, 1H), 7.25 (d, J=5.2 Hz, 2H), 7.29(dd, J=7.6, 4.9 Hz, 1H), 7.32 (m, 1H), 7.35-7.41 (m, 4H), 7.43-7.48 (m,3H), 7.94 (dd, J=7.6, 1.8 Hz, 1H), 8.45 (dd, J=4.3, 1.5 Hz, 2H), 8.58(dd, J=4.9, 1.8 Hz, 1H), 10.45 (s, 1H)

N-(3-Phenoxyphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-199)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.41 (s, 2H), 6.77 (m, 1H), 7.03-7.06 (m, 2H), 7.16 (m, 1H) 7.27 (dd,J=7.6, 4.9 Hz, 1H), 7.33-7.48 (m, 7H), 7.94 (dd, J=7.6, 1.8 Hz, 1H),8.45 (dd, J=4.3, 1.5 Hz, 2H), 8.58 (dd, J=4.9, 1.8 Hz, 1H), 10.45 (s,1H)

N-(3,4-Dichlorophenyl)-2-(4-pyridylmethylthio)benzamide (Compound No.1-200)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.26 (s, 2H), 7.31 (m, 1H), 7.35 (d, J=5.8 Hz, 2H), 7.44 (m, 1H), 7.48(dd, J=7.9, 1.2 Hz, 1H), 7.54 (dd, J=7.3, 1.2 Hz, 1H), 7.62 (s, 1H),7.65 (dd, J=8.9, 2.1 Hz, 1H), 8.10 (d, J=2.1 Hz, 1H), 8.46 (d, J=5.8 Hz,2H), 10.65 (s, 1H)

N-(4-Methylphenyl)-2-(4-pyridylmethylthio)benzamide (Compound No. 1-201)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.27 (s, 3H) 4.25 (s, 2H), 7.14 (d, J=8.2 Hz, 2H), 7.28 (m, 1H), 7.35(d, J=5.8 Hz, 2H), 7.40 (dd, J=7.6 Hz, 1H), 7.45 (m, 1H), 7.50 (d, J=6.7Hz, 1H), 7.61 (d, J=8.2 Hz, 2H), 8.45 (d, J=5.8 Hz, 2H), 10.25 (s, 1H)

N-(3,4-Difluorophenyl)-2-(4-pyridylmethylthio)benzamide (Compound No.1-202)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.26 (s, 2H), 7.30 (m, 1H), 7.35 (d, J=5.8 Hz, 2H), 7.39-7.50 (m, 3H),7.53 (m, 1H), 7.88 (m, 1H), 7.62 (s, 1H), 8.46 (d, J=5.8 Hz, 2H), 10.58(s, 1H)

N-(4-Chloro-3-trifluoromethylphenyl)-2-(4-pyridylmethylthio)benzamide(Compound No. 1-203)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.27 (s, 2H), 7.32 (t, J=7.6 Hz, 1H), 7.36 (d, J=6.1 Hz, 2H), 7.45 (t,J=7.6 Hz, 1H), 7.50 (d, J=7.6 Hz, 1H), 7.58 (d, J=7.6 Hz, 1H), 7.72 (d,J=8.8 Hz, 1H), 7.99 (d, J=8.8 Hz, 1H), 8.33 (s, 1H), 8.45 (d, J=6.1 Hz,2H), 10.80 (s, 1H)

N-(4-Methyl-3-trifluoromethylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-204)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.50 (s, 3H), 4.42 (s, 2H), 7.31 (dd, J=7.6, 4.9 Hz, 1H), 7.40 (d,J=5.6 Hz, 2H), 7.43 (d, J=8.3 Hz, 1H), 7.82 (d, J=8.3 Hz, 1H), 8.01 (dd,J=7.6, 1.2 Hz, 1H), 8.11 (s, 1H), 8.45 (d, J=5.6 Hz, 2H), 8.60 (dd,J=4.9, 1.2 Hz, 1H), 10.68 (s, 1H)

N-(4-Methoxy-3-trifluoromethylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-205)

¹H-NMR (400 MHz, DMSO-d₆)

δ 3.88 (s, 3H), 4.42 (s, 2H), 7.29 (d, J=9.0 Hz, 1H), 7.30 (dd, J=7.6,4.9 Hz, 1H), 7.40 (dd, J=4.4, 1.5 Hz, 2H), 7.88 (dd, J=9.0, 2.2 Hz, 1H),8.01 (dd, J=7.6, 1.7 Hz, 1H), 8.05 (d, J=2.2 Hz, 1H), 8.46 (dd, J=4.4,1.5 Hz, 2H), 8.60 (dd, J=4.9, 1.7 Hz, 1H), 10.58 (s, 1H)

2-(4-Pyridylmethylthio)-N-(3-trifluoromethylphenyl)benzamide (CompoundNo. 1-206)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.27 (s, 2H), 7.31 (m, 1H), 7.36 (d, J=5.9 Hz, 2H), 7.40-7.50 (m, 3H),7.57 (dd, J=7.3, 1.2 Hz, 1H), 7.60 (d, J=7.8 Hz, 1H), 7.92 (d, J=7.8 Hz,1H), 8.23 (s, 1H), 8.45 (d, J=5.9 Hz, 2H), 10.70 (s, 1H)

N-(4-Isopropoxyphenyl)-2-(4-pyridylmethylthio)benzamide (Compound No.1-207)

¹H-NMR (400 MHz, DMSO-d₆)

δ 1.25 (d, J=6.1 Hz, 6H), 4.25 (s, 2H), 4.56 (m, 1H), 6.89 (d, J=9.0 Hz,2H), 7.28 (dd, J=8.1, 6.3 Hz, 1H), 7.36 (d, J=5.9 Hz, 2H), 7.39 (d,J=8.1 Hz, 1H), 7.44 (dd, J=8.1, 7.1 Hz, 1H), 7.48 (d, J=6.3 Hz, 1H),7.60 (d, J=9.0 Hz, 2H), 8.45 (d, J=5.9 Hz, 2H), 10.19 (s, 1H)

N-(3,4-Dimethylphenyl)-2-(4-pyridylmethylthio)benzamide (Compound No.1-208)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.19 (s, 3H), 2.21 (s, 3H), 4.25 (s, 2H), 7.08 (d, J=8.1 Hz, 1H), 7.27(m, 1H), 7.36 (dd, J=4.4, 1.5 Hz, 2H), 7.37-7.53 (m, 5H), 8.45 (dd,J=4.4, 1.5 Hz, 2H), 10.18 (s, 1H)

N-(3-Isoquinolyl)-2-(4-pyridylmethylthio)benzamide (Compound No. 1-209)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.26 (s, 2H), 7.29 (m, 1H), 7.37 (d, J=5.8 Hz, 2H), 7.40-7.44 (m, 2H),7.57 (m, 1H), 7.61 (m, 1H), 7.75 (m, 1H), 7.98 (d, J=8.2 Hz, 1H), 8.08(d, J=8.2 Hz, 1H), 8.46 (d, J=5.8 Hz, 2H), 8.60 (s, 1H), 9.18 (s, 1H),10.98 (s, 1H)

2-(4-Pyridylmethylthio)-N-(4-trifluoromethylphenyl)benzamide (CompoundNo. 1-210)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.26 (s, 2H), 7.31 (m, 1H), 7.35 (d, J=5.8 Hz, 2H), 7.44 (m, 1H), 7.49(d, J=7.3 Hz, 1H), 7.56 (dd, J=7.3, 1.2 Hz, 1H), 7.72 (d, J=8.6 Hz, 2H),7.94 (d, J=8.6 Hz, 2H), 8.45 (d, J=5.8 Hz, 2H), 10.73 (s, 1H)

N-(3-Methyl-5-trifluoromethylphenyl)-2-(4-pyridylmethylthio)benzamide(Compound No. 1-211)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.39 (s, 3H), 4.26 (s, 2H), 7.28-7.33 (m, 2H), 7.35 (d, J=6.1 Hz, 2H),7.40-7.50 (m, 2H), 7.55 (dd, J=7.6, 1.2 Hz, 1H), 7.78 (s, 1H), 7.98 (s,1H), 8.45 (d, J=6.1 Hz, 2H), 10.60 (s, 1H)

N-(4-Isopropyl-3-methylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(Compound No. 1-212)

¹H-NMR (500 MHz, DMSO-d₆)

δ 1.16 (d, J=6.7 Hz, 6H), 2.28 (s, 3H), 3.07 (m, 1H), 4.41 (s, 2H), 7.19(d, J=8.0 Hz, 1H), 7.28 (dd, J=7.6, 4.9 Hz, 1H), 7.40 (dd, J=4.6, 1.8Hz, 2H), 7.45 (d, J=8.0 Hz, 1H), 7.46 (s, 1H), 7.92 (dd, J=7.6, 1.8 Hz,1H), 8.45 (dd, J=4.6, 1.8 Hz, 2H), 8.57 (dd, J=4.9, 1.8 Hz, 1H), 10.30(s, 1H)

N-(3,5-Dimethylphenyl)-2-(2-fluoropyridin-4-ylmethylthio)pyridine-3-carboxamide(Compound No. 1-213)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.26 (s, 6H), 4.46 (s, 2H), 6.76 (s, 1H), 7.18 (s, 1H), 7.29 (dd,J=7.3, 4.6 Hz, 1H), 7.32 (s, 2H), 7.38 (d, J=5.2 Hz, 1H), 7.94 (dd,J=7.3, 1.5 Hz, 1H), 8.13 (d, J=5.2 Hz, 1H), 8.58 (dd, J=4.6, 1.5 Hz,1H), 10.32 (s, 1H)

2-(2-Fluoropyridin-4-ylmethylthio)-N-(4-trifluoromethoxyphenyl)pyridine-3-carboxamide(Compound No. 1-214)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.47 (s, 2H), 7.18 (s, 1H), 7.32 (dd, J=7.6, 4.9 Hz, 1H), 7.35-7.40(m, 3H), 7.81 (d, J=8.2 Hz, 2H), 8.00 (dd, J=7.6, 1.8 Hz, 1H), 8.13 (d,J=5.2 Hz, 1H), 8.61 (dd, J=4.9, 1.8 Hz, 1H), 10.67 (s, 1H)

2-(2-Fluoropyridin-4-ylmethylthio)-N-(5-indanyl)pyridine-3-carboxamide(Compound No. 1-215)

¹H-NMR (500 MHz, DMSO-d₆)

δ 1.98-2.06 (m, 2H), 2.79-2.90 (m, 4H), 4.46 (s, 2H), 7.16-7.20 (m, 2H),7.29 (dd, J=7.3, 4.9 Hz, 1H), 7.38 (dd, J=4.6, 1.5 Hz, 2H), 7.61 (s,1H), 7.95 (dd, J=7.3, 1.5 Hz, 1H), 8.13 (d, J=5.2 Hz, 1H), 8.58 (dd,J=4.9, 1.5 Hz, 1H), 10.35 (s, 1H)

2-(2-Chloropyridin-4-ylmethylthio)-N-(5-indanyl)pyridine-3-carboxamide(Compound No. 1-216)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.01-2.04 (m, 2H), 2.48-2.51 (m, 4H), 4.43 (s, 2H), 7.18 (d, J=8.3 Hz,1H), 7.29 (dd, J=7.6, 4.9 Hz, 1H), 7.38 (d, J=7.7 Hz, 1H), 7.44 (d,J=5.8 Hz, 1H), 7.53 (s, 1H), 7.61 (s, 1H), 7.95 (d, J=7.6 Hz, 1H), 8.29(d, J=5.8 Hz, 1H), 8.58 (dd, J=4.9, 1.5 Hz, 1H), 10.35 (s, 1H)

2-(2-Chloropyridin-4-ylmethylthio)-N-(3-methylphenyl)pyridine-3-carboxamide(Compound No. 1-217)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.30 (s, 3H), 4.43 (s, 2H), 6.94 (d, J=7.3 Hz, 1H), 7.23 (t, J=8.0 Hz,1H), 7.30 (dd, J=7.6, 4.9 Hz, 1H), 7.45 (m, 2H), 7.53-7.55 (m, 2H), 7.96(dd, J=7.6, 1.5 Hz, 1H), 8.29 (d, J=5.2 Hz, 1H), 8.58 (dd, J=4.9, 1.5Hz, 1H), 10.39 (s, 1H)

2-(2-Chloropyridin-4-ylmethylthio)-N-(3,4-dimethylphenyl)pyridine-3-carboxamide(Compound No. 1-218)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.19 (s, 3H), 2.21 (s, 3H), 4.42 (s, 2H), 7.09 (d, J=8.3 Hz, 1H), 7.29(dd, J=7.6, 4.9 Hz, 1H), 7.39 (d, J=8.3 Hz, 1H), 7.44 (dd, J=5.2, 1.6Hz, 1H), 7.48 (s, 1H), 7.53 (d, J=0.6 Hz, 1H), 7.95 (dd, J=7.6, 1.5 Hz,1H), 8.29 (d, J=5.2 Hz, 1H), 8.58 (dd, J=4.9, 1.5 Hz, 1H), 10.31 (s, 1H)

2-(2-Chloropyridin-4-ylmethylthio)-N-(3-isopropylphenyl)pyridine-3-carboxamide(Compound No. 1-219)

¹H-NMR (500 MHz, DMSO-d₆)

δ 1.20 (d, J=6.7 Hz, 6H), 2.87 (m, 1H), 4.43 (s, 2H), 7.00 (d, J=7.6 Hz,1H), 7.26 (t, J=8.0 Hz, 1H), 7.30 (dd, J=7.6, 4.9 Hz, 1H), 7.44 (dd,J=4.9, 1.4 Hz, 1H), 7.51 (m, 1H), 7.53 (m, 1H), 7.59 (s, 1H), 7.98 (dd,J=7.6, 1.5 Hz, 1H), 8.29 (d, J=4.9 Hz, 1H), 8.58 (dd, J=4.9, 1.5 Hz,1H), 10.40 (s, 1H)

N-(4-Bromo-3-methylphenyl)-2-(2-chloropyridin-4-ylmethylthio)pyridine-3-carboxamide(Compound No. 1-220)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.34 (s, 3H), 4.43 (s, 2H), 7.31 (dd, J=7.3, 4.9 Hz, 1H), 7.42-7.46(m, 2H), 7.51-7.54 (m, 2H), 7.72 (d, J=2.1 Hz, 1H), 7.79 (dd, J=7.3, 1.8Hz, 1H), 8.29 (d, J=4.9 Hz, 1H), 8.59 (dd, J=4.9, 1.8 Hz, 1H), 10.53 (s,1H)

2-(2-Chloropyridin-4-ylmethylthio)-N-(4-n-propylphenyl)pyridine-3-carboxamide(Compound No. 1-221)

¹H-NMR (500 MHz, DMSO-d₆)

δ 0.88 (t, J=7.3 Hz, 3H), 1.54-1.59 (m, 2H), 2.50-2.54 (m, 2H), 4.43 (s,2H), 7.16 (d, J=8.6 Hz, 2H), 7.30 (dd, J=7.6, 4.9 Hz, 1H), 7.44 (dd,J=4.9, 1.4 Hz, 1H), 7.53 (d, J=0.6 Hz, 1H), 7.57-7.60 (m, 2H), 7.96 (dd,J=7.6, 1.5 Hz, 1H), 8.29 (m, 1H), 8.58 (dd, J=4.9, 1.5 Hz, 1H), 10.39(s, 1H)

2-(2-Chloropyridin-4-ylmethylthio)-N-(4-fluoro-3-methylphenyl)pyridine-3-carboxamide(Compound No. 1-222)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.23 (s, 3H), 4.43 (s, 2H), 7.12 (t, J=9.2 Hz, 1H), 7.30 (dd, J=7.6,4.9 Hz, 1H), 7.44 (dd, J=5.2, 1.2 Hz, 1H), 7.48 (m, 1H), 7.53 (d, J=0.6Hz, 1H), 7.63 (d, J=4.9 Hz, 1H), 7.97 (dd, J=7.6, 1.5 Hz, 1H), 8.30 (d,J=5.2 Hz, 1H), 8.59 (dd, J=4.9, 1.5 Hz, 1H), 10.45 (s, 1H)

N-(4-tert-Butylphenyl)-2-(2-chloropyridin-4-ylmethylthio)pyridine-3-carboxamide(Compound No. 1-223)

¹H-NMR (500 MHz, DMSO-d₆)

δ 1.27 (s, 9H), 4.43 (s, 2H), 7.30 (dd, J=7.6, 4.9 Hz, 1H), 7.36 (d,J=8.9 Hz, 2H), 7.44 (dd, J=5.2, 1.5 Hz, 1H), 7.53 (d, J=0.9 Hz, 1H),7.58-7.61 (m, 2H), 7.96 (dd, J=7.6, 1.8 Hz, 1H), 8.30 (d, J=5.2 Hz, 1H),8.58 (dd, J=4.9, 1.8 Hz, 1H), 10.40 (s, 1H)

N-(4-Chlorophenyl)-2-(2-chloropyridin-4-ylmethylthio)pyridine-3-carboxamide(Compound No. 1-224)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.43 (s, 2H), 7.31 (dd, J=7.6, 4.8 Hz, 1H), 7.41-7.45 (m, 3H), 7.53(s, 1H), 7.73 (d, J=8.9 Hz, 2H), 8.00 (dd J=7.6, 1.8 Hz, 1H), 8.30 (d,J=5.1 Hz, 1H), 8.60 (dd, J=4.8, 1.8 Hz, 1H), 10.61 (s, 1H)

N-(3-Chlorophenyl)-2-(2-chloropyridin-4-ylmethylthio)pyridine-3-carboxamide(Compound No. 1-225)

¹H-NMR (400 MHz, DMSO-d₆)

δ4.44 (s, 2H), 7.19 (m, 1H), 7.31-7.45 (m, 3H), 7.54 (s, 1H), 7.59 (m,1H), 7.90 (m, 1H), 8.01 (m, 1H), 8.29 (d, J=5.1 Hz, 1H), 8.61 (dd,J=4.9, 1.7 Hz, 1H), 10.66 (s, 1H)

2-(2-Chloropyridin-4-ylmethylthio)-N-(3,5-dimethylphenyl)pyridine-3-carboxamide(Compound No. 1-226)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.26 (s, 6H), 4.43 (s, 2H), 6.77 (d, J=0.7 Hz, 1H), 7.28-7.32 (m, 3H),7.44 (dd, J=5.1, 1.5 Hz, 1H), 7.53 (dd, J=1.5, 0.7 Hz, 1H), 7.95 (dd,J=7.6, 1.7 Hz, 1H), 8.30 (dd, J=5.1, 0.7 Hz, 1H), 8.58 (dd, J=4.8, 1.7Hz, 1H), 10.33 (s, 1H)

2-(2-Chloropyridin-4-ylmethylthio)-N-(4-trifluoromethoxyphenyl)pyridine-3-carboxamide(Compound No. 1-227)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.44 (s, 2H), 7.31-7.45 (m, 4H), 7.54 (d, J=0.7 Hz, 1H), 7.81 (dd,J=7.1, 2.0 Hz, 2H), 8.01 (dd, J=7.6, 1.8 Hz, 1H), 8.30 (d, J=5.1 Hz,1H), 8.61 (dd, J=4.8, 1.8 Hz, 1H), 10.68 (s, 1H)

2-(3-Chloropyridin-4-ylmethylthio)-N-(3,5-dimethylphenyl)pyridine-3-carboxamide(Compound No. 1-228)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.25 (s, 6H), 4.50 (s, 2H), 6.76 (s, 1H), 7.30 (dd, J=7.6, 4.9 Hz,1H), 7.32 (s, 2H), 7.59 (d, J=4.9 Hz, 1H), 7.97 (dd, J=7.6, 1.5 Hz, 1H),8.42 (d, J=4.9 Hz, 1H), 8.58-8.60 (m, 2H), 10.32 (s, 1H)

2-(2,6-Dichloropyridin-4-ylmethylthio)-N-(3,5-dimethylphenyl)pyridine-3-carboxamide(Compound No. 1-229)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.26 (s, 6H), 4.43 (s, 2H), 6.77 (s, 1H), 7.30-7.33 (m, 3H), 7.59 (s,2H), 7.97 (dd, J=7.4, 1.8 Hz, 1H), 8.59 (dd, J=4.8, 1.5 Hz, 1H), 10.32(s, 1H)

2-(2-Bromopyridin-4-ylmethylthio)-N-(3,5-dimethylphenyl)pyridine-3-carboxamide(Compound No. 1-230)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.26 (s, 6H), 4.41 (s, 2H), 6.76 (d, J=0.7 Hz, 1H), 7.29 (dd, J=7.6,4.8 Hz, 1H), 7.32 (s, 2H), 7.47 (dd, J=5.1, 1.4 Hz, 1H), 7.67 (s, 1H),7.93 (dd, J=7.6, 1.7 Hz, 1H), 8.27 (dd, J=5.1, 1.7 Hz, 1H), 8.58 (dd,J=4.8, 1.7 Hz, 1H), 10.32 (s, 1H)

N-(3,5-Dimethylphenyl)-2-(2-methylthiopyridin-4-ylmethylthio)pyridine-3-carboxamide(Compound No. 1-231)

¹H-NMR (500 MHz, CDCl₃)

δ 2.32 (s, 6H), 2.53 (s, 3H), 4.38 (s, 2H), 6.81 (s, 1H), 7.02 (dd,J=5.0, 1.3 Hz, 1H), 7.12 (dd, J=7.6, 4.9 Hz, 1H), 7.24-7.26 (m, 3H),7.75 (s, 1H), 7.86 (dd, J=7.6, 1.5 Hz, 1H), 8.32 (d, J=5.0 Hz, 1H), 8.52(dd, J=4.9, 1.5 Hz, 1H)

N-(4-Chlorophenyl)-2-(2-methylthiopyridin-4-ylmethylthio)pyridine-3-carboxamide(Compound No. 1-232)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.46 (s, 3H), 4.37 (s, 2H), 7.12 (dd, J=4.9, 1.5 Hz, 1H), 7.29-7.31(m, 2H), 7.39-7.41 (m, 2H), 7.71 (d, J=4.5 Hz, 2H), 7.98 (dd, J=7.6, 1.8Hz, 1H), 8.31 (d, J=4.5 Hz, 1H), 8.60 (dd, J=4.9, 1.8 Hz, 1H), 10.60 (s,1H)

N-(3-Chlorophenyl)-2-(2-cyanopyridin-4-ylmethylthio)pyridine-3-carboxamide(Compound No. 1-233)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.48 (s, 2H), 7.19 (ddd, J=7.8, 1.9, 0.9 Hz, 1H), 7.31 (dd, J=7.6, 4.9Hz, 1H), 7.39 (d, J=8.1 Hz, 1H), 7.58 (d, J=8.1 Hz, 1H), 7.77 (dd,J=4.9, 1.7 Hz, 1H), 7.89 (t, J=1.9 Hz, 1H), 8.02 (dd, J=7.6, 1.7 Hz,1H), 8.06 (d, J=0.9 Hz, 1H), 8.59-8.64 (m, 2H), 10.65 (s, 1H)

2-(2-Cyanopyridin-4-ylmethylthio)-N-(3-methylphenyl)pyridine-3-carboxamide(Compound No. 1-234)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.30 (s, 3H), 4.47 (s, 2H), 6.94 (d, J=7.7 Hz, 1H), 7.23 (d, J=7.7 Hz,1H), 7.30 (dd, J=7.6, 4.9 Hz, 1H), 7.46 (d, J=8.0 Hz, 1H), 7.55 (s, 1H),7.77 (dd, J=5.1, 1.7 Hz, 1H), 7.98 (dd, J=7.6, 1.7 Hz, 1H), 8.06 (d,J=1.0 Hz, 1H), 8.58 (dd, J=4.9, 1.7 Hz, 1H), 8.64 (dd, J=5.1, 1.7 Hz,1H), 10.40 (s, 1H)

N-(4-Chlorophenyl)-2-(2-cyanopyridin-4-ylmethylthio)pyridine-3-carboxamide(Compound No. 1-235)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.47 (s, 2H), 7.31 (dd, J=7.6, 4.9 Hz, 1H), 7.41-7.44 (m, 2H),7.72-7.78 (m, 3H), 8.01 (dd, J=7.6, 1.5 Hz, 1H), 8.06 (s, 1H), 8.59-8.64(m, 2H), 10.60 (s, 1H)2-(2-Cyanopyridin-4-ylmethylthio)-N-(3,5-dimethylphenyl)pyridine-3-carboxamide(Compound No. 1-236)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.26 (s, 6H), 4.47 (s, 2H), 6.77 (s, 1H), 7.28-7.32 (m, 3H), 7.77 (dd,J=4.9, 1.5 Hz, 1H), 7.96 (dd, J=7.6, 1.5 Hz, 1H), 8.06 (s, 1H), 8.57(dd, J=4.9, 1.5 Hz, 1H), 8.64 (d, J=5.2 Hz, 1H), 10.31 (s, 1H)

2-(2-Cyanopyridin-4-ylmethylthio)-N-(4-trifluoromethoxyphenyl)pyridine-3-carboxamide(Compound No. 1-237)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.48 (s, 2H), 7.32 (m, 1H), 7.38 (d, J=8.9 Hz, 2H), 7.77 (dd, J=5.2,1.5 Hz, 1H), 7.81 (d, J=8.9 Hz, 2H), 8.02 (dd, J=7.6, 1.5 Hz, 1H), 8.06(s, 1H), 8.60 (dd, J=4.9, 1.5 Hz, 1H), 8.64 (d, J=5.2 Hz, 1H), 10.66 (s,1H)

2-(2-Cyanopyridin-4-ylmethylthio)-N-(4-fluoro-3-methylphenyl)pyridine-3-carboxamide(Compound No. 1-238)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.23 (s, 3H), 4.47 (s, 2H), 7.13 (d, J=9.2 Hz, 1H), 7.30 (dd, J=7.6,4.9 Hz, 1H), 7.49 (m, 1H), 7.63 (m, 1H), 7.77 (dd, J=4.9, 1.8 Hz, 1H),7.98 (dd, J=7.6, 1.8 Hz, 1H), 8.06 (s, 1H), 8.58 (dd, J=4.9, 1.8 Hz,1H), 8.63 (dd, J=4.9, 0.7 Hz, 1H), 10.44 (s, 1H)

2-(2-Cyanopyridin-4-ylmethylthio)-N-(5-indanyl)pyridine-3-carboxamide(Compound No. 1-239)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.01 (q, J=7.4 Hz, 2H), 2.81-2.87 (m, 4H), 4.46 (s, 2H), 7.18 (d,J=8.1 Hz, 1H), 7.29 (dd, J=7.6, 4.7 Hz, 1H), 7.39 (d, J=8.1 Hz, 1H),7.61 (s, 1H), 7.77 (dd, J=5.0, 1.7 Hz, 1H), 7.96 (dd, J=7.6, 1.5 Hz,1H), 8.06 (d, J=0.9 Hz, 1H), 8.57 (dd, J=4.7, 1.5 Hz, 1H), 8.63 (dd,J=5.0, 0.9 Hz, 1H), 10.34 (s, 1H)

N-(4-tert-Butylphenyl)-2-(2-cyanopyridin-4-ylmethylthio)pyridine-3-carboxamide(Compound No. 1-240)

¹H-NMR (400 MHz, DMSO-d₆)

δ 1.28 (s, 9H), 4.47 (s, 2H), 7.30 (dd, J=7.6, 4.9 Hz, 1H), 7.37 (dd,J=6.6, 2.0 Hz, 2H), 7.61 (d, J=8.6 Hz, 2H), 7.77 (dd, J=4.9, 1.7 Hz,1H), 7.97 (dd, J=7.7, 1.6 Hz, 1H), 8.06 (d, J=1.0 Hz, 1H), 8.58 (dd,J=4.9, 1.7 Hz, 1H), 8.63 (dd, J=5.0, 0.6 Hz, 1R), 10.40 (s, 1H)

2-(2-Ethoxycarbonylpyridin-4-ylmethylthio)-N-(3,5-dimethylphenyl)-pyridine-3-carboxamide(Compound No. 1-241)

¹H-NMR (400 MHz, DMSO-d₆)

δ 1.31 (t, J=7.1 Hz, 3H), 2.25 (s, 6H), 4.32 (q, J=7.1 Hz, 2H), 4.49 (s,2H), 6.76 (s, 1H), 7.29 (m, 1H), 7.32 (s, 2H), 7.66 (dd, J=4.9, 1.7 Hz,1H), 7.94 (dd, J=7.6, 1.7 Hz, 1H), 8.10 (d, J=1.0 Hz, 1H), 8.56-8.59 (m,2H), 10.31 (s, 1H)

N-(4-Chlorophenyl)-3-(4-pyridylmethylthio)pyrazine-2-carboxamide(Compound No. 1-242)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.39 (s, 2H), 7.41 (dd, J=6.7, 2.1 Hz, 2H), 7.43 (dd, J=4.6, 1.5 Hz,2H), 7.86 (dd, J=6.7, 2.1 Hz, 2H), 8.47 (dd, J=4.6, 1.5 Hz, 2H), 8.50(d, J=2.5 Hz, 1H), 8.74 (d, J=2.5 Hz, 1H), 10.84 (br s, 1H)

N-(3,5-Dimethylphenyl)-3-(4-pyridylmethylthio)pyrazine-2-carboxamide(Compound No. 1-243)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.26 (s, 6H), 4.39 (s, 2H), 6.78 (s, 1H), 7.44 (dd, J=4.4, 1.7 Hz,2H), 7.45 (s, 2H), 8.48 (dd, J=4.4, 1.7 Hz, 2H), 8.49 (d, J=2.5 Hz, 1H),8.74 (d, J=2.5 Hz, 1H), 10.46 (br s, 1H)

N-(4-Methoxyphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-244)

¹H-NMR (400 MHz, DMSO-d₆)

δ 3.74 (s, 3H), 4.28 (s, 2H), 6.91 (dd, J=6.8, 2.2 Hz, 2H), 7.23 (d,J=6.4 Hz, 1H), 7.34 (dd, J=4.4, 1.5 Hz, 2H), 7.53 (dd, J=6.8, 2.2 Hz,2H), 7.81 (d, J=6.4 Hz, 1H), 8.46 (dd, J=4.4, 1.5 Hz, 2H), 9.87 (s, 1H)

N-(4 Fluorophenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-245)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.28 (s, 2H), 7.18 (d, J=9.0 Hz, 2H), 7.24 (d, J=5.4 Hz, 1H), 7.34 (d,J=4.7 Hz, 2H), 7.65 (d, J=9.0 Hz, 2H), 7.84 (d, J=5.4 Hz, 1H), 8.45 (dd,J=4.7, 1.5 Hz, 2H), 10.04 (s, 1H)

N-(4-Isopropoxyphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-246)

¹H-NMR (500 MHz, DMSO-d₆)

δ 1.25 (d, J=6.1 Hz, 6H), 4.27 (s, 2H), 4.56 (m, 1H), 6.88 (dd, J=7.0,2.1 Hz, 2H), 7.22 (d, J=5.4 Hz, 1H), 7.33 (dd, J=4.5, 1.7 Hz, 2H), 7.50(dd, J=7.0, 2.1 Hz, 2H), 7.80 (d, J=5.4 Hz, 1H), 8.46 (dd, J=4.5, 1.7Hz, 2H), 9.85 (s, 1H)

N-(4-Dimethylaminophenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-247)

¹H-NMR (500 MHz, CDCl₃)

δ 2.95 (s, 6H), 3.99 (s, 2H), 6.73 (dd, J=6.8, 2.2 Hz, 2H), 6.93 (d,J=5.2 Hz, 1H), 7.02 (dd, J=4.3, 1.7 Hz, 2H), 7.42 (dd, J=6.8, 2.2 Hz,2H), 7.44 (d, J=5.2 Hz, 1H), 8.47 (dd, J=4.3, 1.7 Hz, 2H), 9.69 (s, 1H)

N-(3-Fluoro-4-methylphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-248)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.19 (d, J=1.6 Hz, 3H), 4.28 (s, 2H), 7.22 (m, 1H), 7.25 (d, J=5.2 Hz,1H), 7.32 (m, 1H), 7.34 (dd, J=4.3, 1.5 Hz, 2H), 7.54 (dd, J=12.2, 2.1Hz, 1H), 7.84 (d, J=5.2 Hz, 1H), 8.46 (dd, J=4.3, 1.5 Hz, 2H), 10.08 (s,1H)

N-(3 Chlorophenyl)3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-249)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.00 (s, 2H), 6.98 (d, J=5.2 Hz, 1H), 7.01 (dd, J=4.5, 1.6 Hz, 2H),7.12 (ddd, J=8.1, 2.0, 0.9 Hz, 1H), 7.28 (m, 1H), 7.42 (ddd, J=8.1, 2.0,0.9 Hz, 1H), 7.52 (d, J=5.2 Hz, 1H), 7.64 (t, J=2.0 Hz, 1H), 8.47 (d,J=4.5 Hz, 2H), 9.90 (s, 1H)

N-(4 Chlorophenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-250)

¹H-NMR (500 MHz, DMSO-d₆)

δ 3.99 (s, 2H), 6.98-7.00 (m, 3H), 7.31 (dd, J=6.9, 2.0 Hz, 2H),7.48-7.50 (m, 3H), 8.46 (dd, J=4.4, 1.8 Hz, 2H), 9.87 (s, 1H)

3-(2-Chloropyridin-4-ylmethylthio)-N-(3,5-dimethylphenyl)thiophene-2-carboxamide(Compound No. 1-251)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.25 (s, 6H), 4.28 (s, 2H), 6.75 (d, J=0.6 Hz, 1H), 7.23-7.25 (m, 3H),7.32 (d, J=5.2 Hz, 1H), 7.45 (d, J=0.9 Hz, 1H), 7.84 (d, J=5.2 Hz, 1H),8.28 (m, 1H), 9.86 (s, 1H)

N-(4-Fluoro-3-methylphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-252)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.23 (s, 3H), 4.28 (s, 2H), 7.10 (t, J=9.2 Hz, 1H), 7.23 (d, J=5.2 Hz,1H), 7.34 (dd, J=4.3, 1.5 Hz, 2H), 7.45 (m, 1H), 7.55 (dd, J=7.0, 2.1Hz, 1H), 7.83 (d, J=5.2 Hz, 1H), 8.46 (dd, J=4.3, 1.5 Hz, 2H), 9.96 (s,1H)

N-(3,4-Dimethylphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-253)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.18 (s, 3H), 2.21 (s, 3H), 4.27 (s, 2H), 7.08 (d, J=8.3 Hz, 1H), 7.23(d, J=5.2 Hz, 1H), 7.33 (dd, J=4.3, 1.5 Hz, 2H), 7.35 (dd, J=8.3, 2.1Hz, 1H), 7.40 (d, J=2.1 Hz, 1H), 7.81 (d, J=5.2 Hz, 1H), 8.45 (dd,J=4.3, 1.5 Hz, 2H), 9.84 (s, 1H)

3-(4-Pyridylmethylthio)-N-(3-trifluoromethoxyphenyl)thiophene-2-carboxamide(Compound No. 1-254)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.30 (s, 2H), 7.08 (dt, J=8.2, 1.2 Hz, 1H), 7.26 (d, J=5.2 Hz, 1H),7.35 (dd, J=4.6, 1.5 Hz, 2H), 7.46 (t, J=8.2 Hz, 1H), 7.63 (dt, J=8.2,1.2 Hz, 1H), 7.79 (br s, 1H), 7.87 (d, J=5.2 Hz, 1H), 8.46 (dd, J=4.6,1.5 Hz, 2H), 10.25 (s, 1H)

3-(4-Pyridylmethylthio)-N-(4-trifluoromethylphenyl)thiophene-2-carboxamide(Compound No. 1-255)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.01 (s, 2H), 7.00 (dd, J=4.3, 1.5 Hz, 2H), 7.01 (d, J=5.2 Hz, 1H),7.54 (d, J=5.2 Hz, 1H), 7.61 (d, J=8.6 Hz, 2H), 7.67 (d, J=8.6 Hz, 2H),8.45 (dd, J=4.3, 1.5 Hz, 2H), 10.03 (s, 1H)

N-(4-tert-Butylphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-256)

¹H-NMR (500 MHz, DMSO-d₆)

δ 1.27 (s, 9H), 4.28 (s, 2H), 7.23 (d, J=5.2 Hz, 1H), 7.34 (dd, J=4.3,1.5 Hz, 2H), 7.35 (d, J=8.6 Hz, 2H), 7.54 (d, J=8.6 Hz, 2H), 7.82 (d,J=5.2 Hz, 1H), 8.46 (dd, J=4.3, 1.5 Hz, 2H), 9.93 (s, 1H)

N-(3,4-Dichlorophenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-257)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.30 (s, 2H), 7.26 (d, J=5.2 Hz, 1H), 7.35 (dd, J=4.6, 1.5 Hz, 2H),7.59 (d, J=8.9 Hz, 1H), 7.62 (dd, J=8.9, 2.1 Hz, 1H), 7.87 (d, J=5.2 Hz,1H), 8.01 (d, J=2.1 Hz, 1H), 8.46 (dd, J=4.6, 1.5 Hz, 2H), 10.24 (s, 1H)

N-(4-Methylphenyl) 3 (4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-258)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.27 (s, 3H), 4.28 (s, 2H), 7.14 (d, J=8.3 Hz, 2H), 7.23 (d, J=5.2 Hz,1H), 7.33 (dd, J=4.3, 1.5 Hz, 2H), 7.51 (d, J=8.3 Hz, 2H), 7.82 (d,J=5.2 Hz, 1H), 8.45 (dd, J=4.3, 1.5 Hz, 2H), 9.91 (s, 1H)

N-(3-Methoxyphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-259)

¹H-NMR (500 MHz, DMSO-d₆)

δ 3.75 (s, 3H), 4.28 (s, 2H), 6.68 (ddd, J=7.6, 2.4, 1.5 Hz, 1H),7.19-7.23 (m, 2H), 7.25 (d, J=5.2 Hz, 1H), 7.32 (dd, J=2.4, 1.5 Hz, 1H),7.34 (dd, J=4.6, 1.5 Hz, 2H), 7.83 (d, J=5.2 Hz, 1H), 8.46 (dd, J=4.6,1.5 Hz, 2H), 9.97 (s, 1H)

N-[2-(4-Chlorophenyl)ethyl]-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-260)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.79 (t, J=7.0 Hz, 2H), 3.41 (td, J=7.0, 5.5 Hz, 2H), 4.21 (s, 2H),7.14 (d, J=5.2 Hz, 1H), 7.26 (dd, J=6.4, 2.1 Hz, 2H), 7.28 (dd, J=4.3,1.5 Hz, 2H), 7.34 (dd, J=6.4, 2.4 Hz, 2H), 7.71 (d, J=5.2 Hz, 1H), 8.07(t, J=5.5 Hz, 1H), 8.47 (dd, J=4.3, 1.5 Hz, 2H)

N-(4-Morpholinophenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-261)

¹H-NMR (400 MHz, DMSO-d₆)

δ 3.07 (t, J=4.9 Hz, 4H), 3.74 (t, J=4.9 Hz, 4H), 4.27 (s, 2H), 6.92 (d,J=9.3 Hz, 2H), 7.22 (d, J=5.1 Hz, 1H), 7.33 (dd, J=4.4, 1.5 Hz, 2H),7.48 (d, J=9.3 Hz, 2H), 7.80 (d, J=5.1 Hz, 1H), 8.45 (dd, J=4.4, 1.5 Hz,2H), 9.81 (s, 1H)

N-(4-Chlorophenyl)-N-methyl-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-262)

¹H-NMR (500 MHz, DMSO-d₆)

δ 3.42 (s, 3H), 4.03 (s, 2H), 6.67 (d, J=5.1 Hz, 1H), 7.05 (dd, J=8.5Hz, 2H), 7.16 (d, J=5.1 Hz, 1H), 7.23-7.30 (m, 4H), 8.52 (d, J=5.9 Hz,2H)

N-(3-Methylphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-263)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.30 (s, 3H), 4.28 (s, 2H), 6.92 (d, J=7.2 Hz, 1H), 7.19-7.25 (m, 2H),7.33 (dd, J=4.4, 1.7 Hz, 2H), 7.41 (d, J=8.0 Hz, 1H), 7.47 (s, 1H), 7.83(d, J=5.1 Hz, 1H), 8.46 (dd, J=4.4, 1.7 Hz, 2H), 9.92 (s, 1H)

N-(3-tert-Butylphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-264)

¹H-NMR (500 MHz, DMSO-d₆)

δ 1.28 (s, 9H), 4.28 (s, 2H), 7.13 (ddd, J=8.0, 1.9, 1.0 Hz, 1H),7.24-7.27 (m, 2H), 7.34 (dd, J=4.3, 1.5 Hz, 2H), 7.49 (ddd, J=8.0, 1.9,1.0 Hz, 1H), 7.63 (m, 1H), 7.83 (d, J=5.2 Hz, 1H), 8.46 (dd, J=4.3, 1.5Hz, 2H), 9.93 (s, 1H)

N-Phenyl-3-(4-pyridylmethylthio)thiophene-2-carboxamide (Compound No.1-265)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.28 (s, 2H), 7.11 (m, 1H), 7.24 (d, J=5.5 Hz, 1H), 7.32-7.36 (m, 4H),7.61-7.64 (m, 2H), 7.83 (m, 1H), 8.46 (dd, J=4.4, 1.6 Hz, 2H), 10.00 (s,1H)

N-[2-(4-Methoxyphenyl)ethyl]-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-266)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.72 (t, J=7.3 Hz, 2H), 3.35-3.40 (m, 2H), 3.71 (s, 3H), 4.20 (s, 2H),6.86 (dd, J=6.6, 1.9 Hz, 2H), 7.14-7.16 (m, 3H), 7.27 (dd, J=4.4, 1.7Hz, 2H), 7.71 (d, J=5.1 Hz, 1H), 8.06 (t, J=5.6 Hz, 1H), 8.46 (dd,J=4.4, 1.7 Hz, 2H)

N-(3-Chloro-4-fluorophenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-267)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.29 (s, 2H), 7.25 (d, J=2.0 Hz, 1H), 7.36 (dd, J=4.4, 1.7 Hz, 2H),7.40 (m, 1H), 7.60 (m, 1H), 7.86 (d, J=5.2 Hz, 1H), 7.94 (dd, J=7.0, 2.6Hz, 1H), 8.47 (dd, J=4.4, 1.7 Hz, 2H), 10.17 (s, 1H)

N-(4-Chloro-3-methylphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-268)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.32 (s, 3H), 4.28 (s, 2H), 7.24 (d, J=5.4 Hz, 1H), 7.33-7.37 (m, 3H),7.50 (dd, J=8.5, 2.4 Hz, 1H), 7.64 (d, J=2.4 Hz, 1H), 7.84 (d, J=5.4 Hz,1H), 8.46 (dd, J=4.4, 1.7 Hz, 2H), 10.04 (s, 1H)

N-(3,4-Difluorophenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-269)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.29 (s, 2H), 7.25 (d, J=5.2 Hz, 1H), 7.35 (dd, J=4.3, 1.5 Hz, 2H),7.40-7.43 (m, 2H), 7.78 (m, 1H), 7.86 (d, J=5.2 Hz, 1H), 8.46 (dd,J=4.3, 1.5 Hz, 2H), 10.18 (s, 1H)

N-(4-n-Propylphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-270)

¹H-NMR (400 MHz, DMSO-d₆)

δ 0.89 (t, J=7.3 Hz, 3H), 1.55-1.60 (m, 2H), 2.49-2.51 (m, 2H), 4.28 (s,2H), 7.14 (d, J=8.5 Hz, 2H), 7.23 (d, J=5.4 Hz, 1H), 7.33 (dd, J=4.4,1.7 Hz, 2H), 7.51-7.53 (m, 2H), 7.82 (d, J=5.4 Hz, 1H), 8.45 (dd, J=4.4,1.7 Hz, 2H), 9.93 (s, 1H)

N-(4-Bromophenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-272)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.29 (s, 2H), 7.25 (d, J=5.2 Hz, 1H), 7.34 (dd, J=4.4, 1.7 Hz, 2H),7.52 (dd, J=6.8, 2.0 Hz, 2H), 7.62 (dd, J=6.8, 2.0 Hz, 2H), 7.85 (d,J=5.2 Hz, 1H), 8.46 (dd, J=4.4, 1.7 Hz, 2H), 10.12 (s, 1H)

3-(4-Pyridylmethylthio)-N-(4-trifluoromethoxyphenyl)thiophene-2-carboxamide(Compound No. 1-273)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.29 (s, 2H), 7.25 (d, J=5.2 Hz, 1H), 7.34-7.36 (m, 4H), 7.73-7.77 (m,2H), 7.85 (d, J=5.2 Hz, 1H), 8.46 (dd, J=4.4, 1.5 Hz, 2H), 10.18 (s, 1H)

N-(3-Isoquinolyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-274)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.34 (s, 2H), 7.28-7.31 (m, 3H), 7.58 (m, 1H), 7.75 (m, 1H), 7.92-7.96(m, 2H), 8.10 (d, J=7.9 Hz, 1H), 8.39 (dd, J=4.2, 1.5 Hz, 2H), 8.47 (s,1H), 9.20 (s, 1H), 10.58 (s, 1H)

N-(3,5-Dimethylphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-275)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.25 (s, 6H), 4.28 (s, 2H), 6.74 (d, J=0.7 Hz, 1H), 7.23 (d, J=5.1 Hz,1H), 7.25 (d, J=0.7 Hz, 2H), 7.33 (dd, J=4.4, 1.5 Hz, 2H), 7.82 (d,J=5.1 Hz, 1H), 8.45 (dd, J=4.4, 1.5 Hz, 2H), 9.85 (s, 1H)

3-(4-Pyridylmethylthio)-N-(3-trifluoromethylphenyl)thiophene-2-carboxamide(Compound No. 1-276)

¹H-NMR (400 MHz, CDCl₃)

δ 4.02 (s, 2H), 7.00 (d, J=5.1 Hz, 1H), 7.01 (d, J=5.1 Hz, 2H), 7.40 (d,J=7.8 Hz, 1H), 7.48 (m, 1H), 7.54 (d, J=5.1 Hz, 1H), 7.76 (s, 1H), 7.79(d, J=5.1 Hz, 1H), 8.47 (d, J=5.1 Hz, 2H), 10.00 (br s, 1H)

N-(3,5-Dichlorophenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-277)

¹H-NMR (400 MHz, CDCl₃)

δ 4.01 (s, 2H), 6.99-7.01 (m, 3H), 7.25-7.26 (m, 2H), 7.48 (m, 1H), 7.54(d, J=5.1 Hz, 1H), 8.48-8.49 (m, 2H), 9.93 (br s, 1H)

N-(3-Chloro-4-methylphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-278)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.29 (s, 3H), 4.29 (s, 2H), 7.25 (d, J=5.1 Hz, 1H), 7.30 (d, J=8.3 Hz,1H), 7.35 (dd, J=4.4, 1.5 Hz, 2H), 7.47 (dd, J=8.3, 2.0 Hz, 1H), 7.80(d, J=2.0 Hz, 1H), 7.85 (d, J=5.1 Hz, 1H), 8.46 (dd, J=4.4, 1.5 Hz, 2H),10.07 (s, 1H)

N-(2,2-Dimethylpropyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-279)

¹H-NMR (500 MHz, CDCl₃)

δ 0.95 (s, 9H), 3.18 (d, J=6.1 Hz, 2H), 3.97 (s, 2H), 6.89 (d, J=5.2 Hz,1H), 7.02 (dd, J=4.3, 1.5 Hz, 2H), 7.41 (d, J=5.2 Hz, 1H), 7.91 (br s,1H), 8.51 (dd, J=4.3, 1.5 Hz, 2H)

2-(Piperidine-1-yl)carbonyl-3-(4-pyridylmethylthio)thiophene (CompoundNo. 1-280)

¹H-NMR (500 MHz, CDCl₃)

δ 1.66-1.69 (m, 6H), 3.47-3.50 (m, 4H), 3.98 (s, 2H), 6.71 (d, J=5.0 Hz,1H), 7.17 (dd, J=4.6, 1.5 Hz, 2H), 7.23 (d, J=5.0 Hz, 1H), 8.49 (dd,J=4.6, 1.5 Hz, 2H)

N-Cyclohexyl-3-(4-pyridylmethylthio)thiophene-2-carboxamide (CompoundNo. 1-281)

¹H-NMR (500 MHz, CDCl₃)

δ1.19-1.29 (m, 4H), 1.37-1.46 (m, 2H), 1.59-1.63 (m, 2H), 1.67-1.72 (m,2H), 3.93 (m, 1H), 3.96 (s, 2H), 6.89 (d, J=5.2 Hz, 1H), 7.02 (dd,J=4.3, 1.5 Hz, 2H), 7.39 (d, J=5.2 Hz, 1H), 7.80 (d, J=6.7 Hz, 1H), 8.51(dd, J=4.3, 1.5 Hz, 2H)

N-(4-Bromo-3-methylphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 1-282)

¹H-NMR (500 MHz, CDCl₃)

δ 2.40 (s, 3H), 4.00 (s, 2H), 6.98 (d, J=5.1 Hz, 1H), 7.01 (dd, J=4.4,1.7 Hz, 2H), 7.25 (dd, J=8.6, 2.4 Hz, 1H), 7.47-7.51 (m, 3H), 8.47 (dd,J=4.4, 1.7 Hz, 2H), 9.82 (br s, 1H)

N-(5-Indanyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide (CompoundNo. 1-283)

¹H-NMR (400 MHz, DMSO-d₆)

δ 1.98-2.05 (m, 2H), 2.82-2.85 (m, 4H), 4.27 (s, 2H), 7.16 (d, J=8.1 Hz,1H), 7.23 (d, J=5.1 Hz, 1H), 7.32-7.34 (m, 3H), 7.52 (s, 1H), 7.81 (d,J=5.1 Hz, 1H), 8.45-8.46 (m, 2H), 9.89 (s, 1H).

N-(4 Chlorophenyl)-2-(4-pyridylmethylthio)thiophene-3-carboxamide(Compound No. 1-284)

¹H-NMR (400 MHz, DMSO-d₆)

δ 4.25 (s, 2H), 7.34 (dd, J=4.4, 1.6 Hz, 2H), 7.40 (dd, J=6.9, 2.2 Hz,2H), 7.56 (s, 2H), 7.74 (dd, J=6.9, 2.2 Hz, 2H), 8.48 (dd, J=4.4, 1.6Hz, 2H), 10.10 (s, 1H)

N-(3-Methylphenyl)-2-(4-pyridylmethylthio)thiophene-3-carboxamide(Compound No. 1-285)

¹H-NMR (400 MHz, DMSO-d₆)

δ 2.30 (s, 3H), 4.25 (s, 2H), 6.91 (d, J=7.8 Hz, 1H), 7.21 (t, J=7.8 Hz,1H), 7.35 (dd, J=4.4, 1.7 Hz, 2H), 7.48 (d, J=7.8 Hz, 1H), 7.54-7.56 (m,3H), 8.48 (dd, J=4.4, 1.7 Hz, 2H), 9.91 (s, 1H)

N-(4-Chlorophenyl)-1-methyl-5-(4-pyridylmethylthio)pyrazole-4-carboxamide(Compound No. 1-286)

¹H-NMR (400 MHz, CDCl₃)

δ 3.65 (s, 3H), 3.95 (s, 2H), 6.92 (dd, J=4.4, 1.5 Hz, 2H), 7.32 (dd,J=7.1, 1.7 Hz, 2H), 7.52 (dd, J=7.1, 1.7 Hz, 2H), 8.12 (s, 1H), 8.47(dd, J=4.4, 1.5 Hz, 2H), 8.86 (s, 1H)

N-(5-Indanyl)-2-(4-pyridylmethylthio)thiophene-3-carboxamide (CompoundNo. 1-287)

¹H-NMR (500 MHz, DMSO-d₆)

δ 1.99-2.05 (m, 2H), 2.81-2.87 (m, 4H), 4.24 (s, 2H), 7.17 (d, J=7.9 Hz,1H), 7.33-7.34 (m, 2H), 7.40 (d, J=7.9 Hz, 1H), 7.54 (s, 2H), 7.61 (s,1H), 8.47-8.48 (m, 2H), 9.87 (br s, 1H)

2-(4-Pyridylmethylthio)-N-(4-trifluoromethoxyphenyl)thiophene-3-carboxamide(Compound No. 1-288)

¹H-NMR (500 MHz, DMSO-d₆)

δ 4.25 (s, 2H), 7.34-7.36 (m, 4H), 7.56 (s, 2H), 7.81 (dt, J=9.8, 2.7Hz, 2H), 8.48 (dd, J=4.6, 1.8 Hz, 2H), 10.16 (s, 1H)

N-(4-Bromo-3-methylphenyl)-2-(4-pyridylmethylthio)thiophene-3-carboxamide(Compound No. 1-289)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.34 (s, 3H), 4.25 (s, 2H), 7.34 (dd, J=4.4, 1.7 Hz, 2H), 7.49 (dd,J=8.8, 2.4 Hz, 1H), 7.53 (d, J=8.8 Hz, 1H), 7.55 (d, J=5.5 Hz, 1H), 7.56(d, J=5.5 Hz, 1H), 7.72 (d, J=2.4 Hz, 1H), 8.48 (dd, J=4.4, 1.7 Hz, 2H),10.02 (s, 1H)

2-(4-Pyridylmethylthio)-N-(4-trifluoromethylphenyl)thiophene-3-carboxamide(Compound No. 1-290)

¹H-NMR (500 MHz, CDCl₃)

δ 4.01 (s, 2H), 6.98 (dd, J=4.6, 1.5 Hz, 2H), 7.38 (d, J=5.5 Hz, 1H),7.61 (d, J=8.6 Hz, 2H), 7.65 (d, J=5.5 Hz, 1H), 7.68 (d, J=8.6 Hz, 2H),8.44 (dd, J=4.6, 1.5 Hz, 2H), 9.43 (s, 1H)

N-(3,5-Dimethylphenyl)-2-(4-pyridylmethylthio)thiophene-3-carboxamide(Compound No. 1-291)

¹H-NMR (500 MHz, DMSO-d₆)

δ 2.26 (s, 6H), 4.24 (s, 2H), 6.74 (s, 1H), 7.32-7.35 (m, 4H), 7.53 (d,J=5.4 Hz, 1H), 7.56 (d, J=5.4 Hz, 1H), 8.48-8.49 (m, 2H), 9.82 (s, 1H)

N-(3-Methylphenyl) 4 (4-pyridylmethylthio)thiophene-3 carboxamide(Compound No. 1-292)

¹H-NMR(400MHz,DMSO-d₆)

δ 2.30(s,3H),4.19(s,2H),6.91(d,J=7.3 Hz,1H),7.21(t,J=7.8Hz,1H),7.29(d,J=3.2 Hz,1H),7.39(dd,J=4.5,1.5 Hz,2H),7.47(d,J=8.5Hz,1H),7.56(s,1H),8.29(d,J=3.2 Hz,1H),8.48(dd,J=4.5,1.5Hz,2H),10.10(s,1H)

N-(4-Chlorophenyl)-4-pyridylmethylthio)thiophene-3-carboxamide (CompoundNo. 1-293)

¹H-NMR(400MHz,DMSO-d₆)

δ 4.25(s,2H),6.91(d,J=7.6 Hz,1H),7.21(t,J=7.8 Hz,1H),7.34(dd,J=4.7,1.7Hz,2H),7.48(m,1H),7.54-7.56(m,3H),8.48(dd,J=4.4,1.7 Hz,2H),9.90(s,1H)

N-(4-Chlorophenyl)-3-(4-pyridylmethylthio)benzamide (Compound No. 1-294)

¹H-NMR(500MHz,DMSO-d₆)

δ 4.36(s,2H),7.37(dd,J=4.3,1.8 Hz,2H),7.42(dd,J=6.7,2.2Hz,2H),7.46(d,J=7.6 Hz,1H),7.55(ddd,J=8.0,1.8,1.2Hz,1H),7.75(ddd,J=8.0,1.8,1.2 Hz,1H),7.80(dd,J=6.7,2.2Hz,2H),7.88(m,1H),8.48(dd,J=4.3,1.8 Hz,2H),10.37(s,1H)

N-(4-Chlorophenyl)-4-(4-pyridylmethylthio)benzamide (Compound No. 1-295)

¹H-NMR(400MHz,DMSO-d₆)

δ 4.40(s,2H),7.37-7.48(m,6H),7.79(d,J=8.8 Hz,2H),7.86(d,J=8.8Hz,2H),8.49(dd,J=4.4,1.7 Hz,2H),10.29(s,1H)

N-(Indazol-6-yl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide (CompoundNo. 1-296)

¹H-NMR(400MHz,DMSO-d₆)

δ 4.43(s,2H),7.24(d,J=8.8 Hz,1H),7.30(dd,J=7.6,4.9Hz,1H),7.41(dd,J=4.4,1.5 Hz,2H),7.70(d,J=8.8Hz,1H),7.95-8.00(m,2H),8.21(s,1H),8.45(dd,J=4.4,1.5Hz,2H),8.60(dd,J=4.9,1.7 Hz,1H),10.60(s,1H),12.95(s,1H)

2-(2-Bromopyridin-4-ylmethylthio)-N-(5-indanyl)pyridine-3-carboxamide(Compound No. 1-297)

¹H-NMR(500MHz,DMSO-d₆)

δ 2.00-2.09(m,2H),2.80-2.87(m,4H),4.41(s,2H),7.18(d,J=7.6Hz,1H),7.29(d,J=7.6,4.9 Hz,1H),7.38(d,J=7.6 Hz,1H),7.47(dd,J=4.9,1.8Hz,1H),7.61(s,1H),7.67(s,1H), 7.95(d,J=7.6 Hz,1H),8.27(d,J=5.2Hz,1H),8.58(dd,J=4.9,1.8 Hz,1H),10.36(s,1H)

2-(2-Bromopyridin-4-ylmethylthio)-N-(4-trifluoromethoxyphenyl)pyridine-3-carboxamide(Compound No. 1-298)

¹H-NMR(500MHz,DMSO-d₆)

δ 4.42(s,2H),7.32(dd,J=7.6,4.9 Hz,1H),7.38(d,J=8.7Hz,2H),7.47(dd,J=4.9,1.7 Hz,1H),7.67(s,1H),7.80(d,J=8.7Hz,2H),8.00(dd,J=7.6,1.7 Hz,1H),8.27(d,J=4.9 Hz,1H),8.60(dd,J=4.9,1.7Hz,1H),10.68(s,1H)

2-(2-Benzyloxypyridin-4-ylmethylthio)-N-(3,5-dimethylphenyl)pyridine-3-carboxamide(Compound No. 1-299)

¹H-NMR(500MHz,CDCl₃)

δ2.31(s,6H),4.42(s,2H),5.34(s,2H),6.81(s,1H),6.87(s,1H),6.94(dd,J=5.2,1.5Hz,1H),7.11(dd,J=7.6,4.9Hz,1H),7.26-7.28(m,2H),7.30(d,J=8.6 Hz,1H),7.36(dd,J=8.6,7.0Hz,2H),7.43(d,J=7.0 Hz,2H),7.79(s,1H),7.87(dd,J=7.6,1.5Hz,1H),8.07(d,J=5.2 Hz,1H),8.52(dd,J=4.9,1.5 Hz,1H)

N-(3,5-Dimethylphenyl)-2-(2-methoxypyridin-4-ylmethylthio)pyridine-3-carboxamide(Compound No. 1-300)

¹H-NMR(500MHz,DMSO-d₆)

δ 2.25(s,6H),3.80(s,3H),4.37(s,2H),6.76(s,1H),6.81(d,J=0.5Hz,1H),6.99(dd,J=5.2,1.5 Hz,1H),7.28(dd,J=7.6,4.9Hz,1H),7.32(s,2H),7.92(dd,J=7.6,1.8 Hz,1H),8.04(d,J=5.2Hz,1H),8.58(dd,J=4.9,1.8 Hz,1H),10.31(s,1H)

N-(5-Indanyl)-2-(2-methoxypyridin-4-ylmethylthio)pyridine-3-carboxamide(Compound No. 1-301)

¹H-NMR(500MHz,DMSO-d₆)

δ 1.99-2.03(m,2H),2.81-2.85(m,4H),3.80(s,3H),4.37(s,2H),6.81(d,J=0.6Hz,1H),6.99(dd,J=5.2,1.5 Hz,1H),7.18(d,J=7.9 Hz,1H),7.28(dd,J=7.7,4.8Hz,1H),7.38(d,J=7.9 Hz,1H),7.61(s,1H),7.92(dd,J=7.7,1.5Hz,1H),8.04(dd,J=5.2,0.5 Hz,1H),8.58(dd,J=4.8,1.5 Hz,1H),10.34(s,1H)

N-(3,5-Dimethylphenyl)-2-(2-ethoxypyridin-4-ylmethylthio)pyridine-3-carboxamide(Compound No. 1-302)

¹H-NMR(500MHz,DMSO-d₆)

δ 1.27(d,J=7.0 Hz,3H),2.25(s,6H),4.22-4.27(m,2H),4.37(s,2H),6.76(s,1H),6.77(s,1H), 6.97(dd,J=5.2,1.2 Hz,1H),7.28(dd,J=7.6,4.8Hz,1H),7.32(s,2H),7.92(dd,J=7.6,1.7 Hz,1H),8.02(d,J=5.2Hz,1H),8.58(dd,J=4.8,1.7 Hz,1H),10.31(s,1H)

2-(2-Ethoxypyridin-4-ylmethylthio)-N-(5-indanyl)pyridine-3-carboxamide(Compound No. 1-303)

¹H-NMR(500MHz,DMSO-d₆)

δ 1.27(t,J=7.0 Hz,3H),1.98-2.04(m,2H),2.80-2.86(m,4H),4.25(q,J=7.0Hz,2H),4.37(s,2H),6.77(s,1H),6.97(dd,J=5.2,1.4 Hz,1H),7.18(d,J=7.9Hz,1H),7.28(dd,J=7.6, 4.9 Hz,1H),7.38(d,J=7.9Hz,1H),7.61(s,1H),7.92(dd,J=7.6,1.7 Hz,1H),8.02(d,J=5.2Hz,1H),8.58(dd,J=4.9,1.7 Hz,1H),10.34(s,1H)

N-(3,5-Dimethylphenyl)-2-(2-isopropoxypyridin-4-ylmethylthio)pyridine-3-carboxamide(Compound No. 1-304)

¹H-NMR(500MHz,DMSO-d₆)

δ 1.25(d,J=6.1Hz,6H),2.25(s,6H),4.36(s,2H),5.20(m,1H),6.72(s,1H),6.76(s,1H),6.94(dd,J=5.2,1.2Hz,1H),7.28(dd,J=7.6,4.9 Hz,1H),7.32(s,2H),7.92(dd,J=7.6,1.7Hz,1H),8.02(d,J=5.2 Hz,1H),8.58(dd,J=4.9,1.7 Hz,1H),10.31(s,1H)

N-(5-Indanyl)-2-(2-isopropoxypyridin-4-ylmethylthio)pyridine-3-carboxamide(Compound No. 1-305)

¹H-NMR(500MHz,DMSO-d₆)

δ 1.24(d,J=6.1Hz,6H),1.98-2.04(m,2H),2.80-2.86(m,4H),4.36(s,2H),5.19(m,1H),6.71(s,1H),6.94(dd,J=5.2,1.4 Hz,1H),7.18(d,J=7.6 Hz,1H),7.28(dd,J=7.6, 4.9Hz,1H),7.38(d,J=7.6 Hz,1H),7.61(s,1H),7.93(dd,J=7.6,1.7Hz,1H),8.01(d,J=5.2 Hz,1H), 8.58(dd,J=4.9,1.7 Hz,1H),10.34(s,1H)

N-(3,5-Dimethylphenyl)-2-(2-methoxycarbonylpyridin-4-ylmethylthio)pyridine-3-carboxamide (Compound No. 1-306)

¹H-NMR(400MHz,DMSO-d₆)

δ 2.25(s,6H),3.86(s,3H),4.50(s,2H),6.76(s,1H),7.28(dd,J=7.6, 4.9 Hz,1H),7.32(s,2H),7.66(dd,J=4.9,1.7 Hz,1H),7.93(dd,J=7.6, 1.7Hz,1H),8.11(d,J=0.9 Hz,1H),8.55-8.60(m,2H),10.30(s,1H)

N-(3,5-Dimethylphenyl)-2-(2-methylpyridin-4-ylmethylthio)pyridine-3-carboxamide(Compound No. 1-307)

¹H-NMR(500MHz,DMSO-d₆)

δ 2.25(s,6H),2.41(s,3H),4.37(s,2H),6.76(s,1H),7.19(dd,J=5.2, 1.2 Hz,1H),7.26(s,1H),7.28(dd,J=7.6,4.9 Hz,1H),7.32(s,2H),7.92(dd,J=7.6,1.5Hz,1H),8.31(d,J=4.9 Hz, 1H),8.58(dd,J=4.9,1.5 Hz,1H),10.31(s,1H)

2-(2-Methylpyridin-4-ylmethylthio)-N-(4-trifluoromethoxyphenyl)pyridine-3-carboxamide(Compound No. 1-308)

¹H-NMR(500MHz,DMSO-d₆)

δ 2.41(s,3H),4.38(s,2H),7.19(m,1H),7.26(s,1H),7.31(dd,J=7.6,4.9 Hz,1H),7.37(d,J=8.9 Hz,2H),7.81(d,J=8.9 Hz,2H),7.98(dd,J=7.6,1.8Hz,1H),8.31(d,J=5.2 Hz,1H),8.61(dd,J=4.9,1.8 Hz,1H),10.66(s,1H)

Example 2N-(4-Chlorophenyl)-2-[2-(4-pyridyl)ethylthio]pyridine-3-carboxamide(Compound No. 2-1)

To a suspension of 60% sodium hydride (35 mg, 0.88 mmol) inN,N-dimethylformamide (1 mL), a solution of 4-pyridineethanethiol (104mg, 0.75 mmol) in N,N-dimethylformamide (1.5 mL) and a solution of2-chloro-N-(4-chlorophenyl)pyridine-3-carboxamide (200 mg, 0.75 mmol,Reference compound No. 2-1) in N,N-dimethylformamide (1.5 mL) were addedunder ice-cooling successively. The reaction mixture was stirred at roomtemperature for 2 hours, and then ethyl acetate (40 mL) was addedthereto. The ethyl acetate layer was washed with water (40 mL) and brine(40 mL) and dried over anhydrous magnesium sulfate, then the solvent wasevaporated under reduced pressure. The precipitated solid was filteredoff and washed with diethyl ether:ethyl acetate (3:1). The solid wasdried under reduced pressure to give 240 mg of the target compound as awhite solid. (Yield 88%)

¹H-NMR(400MHz,DMSO-d₆)

δ 2.95(t,J=7.8 Hz,2H),3.43(t,J=7.8 Hz,2H),7.25-7.31(m,3H),7.42(d,J=8.8Hz,2H),7.73(d,J=8.8 Hz,2H),7.94(dd,J=7.6,1.5Hz,1H),8.46(d,J=5.6Hz,2H),8.61(dd,J=7.6,1.5 Hz,1H),10.59(s,1H)

2-(4-Pyridylmethylthio)-N-(4-trifluoromethylsulfonylphenyl)pyridine-3-carboxamide(Compound No. 2-2)

4-Pyridinemethanethiol hydrochloride (0.32 g, 2.0 mmol) and potassiumcarbonate (0.63 g, 4.5 mmol) were added to a solution of2-chloro-N-(4-trifluoromethylsulfonylphenyl)pyridine-3-carboxamide (0.65g, 1.8 mmol, Reference compound No. 2-2) in ethanol (10 mL) under anitrogen atmosphere, then the mixture was stirred at 65° C. for 8 hours.The reaction mixture was diluted with ethyl acetate (100 mL), then theethyl acetate layer was washed with a saturated aqueous sodiumhydrogencarbonate solution (100 mL) and brine (100 mL), and then driedover anhydrous magnesium sulfate. The solvent was evaporated underreduced pressure, then the resulting residue was purified by silica gelcolumn chromatography to give 0.29 g of the target compound as a whitesolid. (Yield 37%)

¹H-NMR(500MHz,DMSO-d₆)

δ 4.44(s,2H),7.34(dd,J=7.6,4.8 Hz,1H),7.40(dd,J=4.6,1.6Hz,2H),8.07(dd,J=7.6, 1.5 Hz,1H),8.13(s,4H),8.45(dd,J=4.6,1.6Hz,2H),8.64(dd,J=4.8,1.5 Hz,1H),11.19(s,1H)

Example 3 N-(4 Chlorophenyl)-2-(4-pyridylmethylsulfinyl)pyridine-3carboxamide (Compound No. 3-1)

A solution of m-chloroperoxybenzoic acid (65%, 160 mg, 0.60 mmol) inchloroform (2 mL) was added to a solution ofN-(4-chlorophenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide (300mg, 0.84 mmol, Compound No. 1-1) in chloroform (18 mL) underice-cooling, then the mixture was stirred at room temperature for 2hours. The precipitated solid in the reaction mixture was filtered off,and dried under reduced pressure to give 220 mg of the target compoundas a pale yellow solid. (Yield 69%)

¹H-NMR(400MHz,DMSO-d₆)

δ 4.25(d,J=12.5 Hz,1H),4.50(d,J=12.5 Hz,1H),7.23(dd,J=4.6,1.5Hz,2H),7.46(d,J=8.8 Hz,2H),7.75(m,1H),7.75(d,J=8.8Hz,2H),8.32(dd,J=7.8,1.5Hz,1H),8.51(dd,J=4.6,1.5Hz,2H),8.87(m,1H),10.80(s,1H)

Example 4N-(4-Chlorophenyl)-2-(1-oxopyridin-4-ylmethylthio)pyridine-3-carboxamide (Compound No. 4-1)

N,N-Diisopropylethylamine (0.16 mL, 0.92 mmol) andO-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (212 mg, 0.56 mmol) were added to a solution of2-(1-oxopyridin-4-ylmethylthio)pyridine-3-carboxylic acid (124 mg, 0.47mmol, Reference compound No. 4-1) and 4-chloroaniline (72 mg, 0.56 mmol)in N,N-dimethylformamide (1.5 mL), then the mixture was stirred at roomtemperature for 15 hours. Ethyl acetate (30 mL) was added to thereaction mixture, then the ethyl acetate layer was washed with asaturated aqueous sodium hydrogencarbonate solution (50 mL) twice andbrine (50 mL) twice, and then dried over anhydrous magnesium sulfate.The solvent was evaporated under reduced pressure, the precipitatedsolid was filtered off and washed with diethyl ether:ethyl acetate(5:1). This solid was dried at 50° C. under reduced pressure to give 113mg of the target compound as a brown solid. (Yield 65%)

¹H-NMR(500MHz,DMSO-d₆)

δ 4.38(s,2H),7.30(dd,J=7.6,4.9 Hz,1H),7.41-7.44(m,4H),7.72(d,J=8.8Hz,2H),7.98 (dd,J=7.6,1.5 Hz,1H),8.09(dd,J=5.2,1.8Hz,2H),8.60(dd,J=4.9,1.8 Hz,1H),10.6(s,1H)

Below compounds (No. 4-2˜11) were obtained by a method similar toExample 4.

N-(6-Indazolyl)-2-(1-oxopyridin-4-ylmethylthio)pyridine-3-carboxamide(Compound No. 4-2)

¹H-NMR(400MHz,DMSO-d₆)

δ 4.39(s,2H),7.24(d,J=8.8 Hz,1H),7.33(m,1H),7.42(d,J=7.1Hz,2H),7.70(d,J=8.8 Hz,1H),7.97-8.01(m,2H),8.01(d,J=7.1Hz,2H),8.21(s,1H),8.60(dd,J=4.9,1.6 Hz,1H),10.60(s,1H),12.97(s,1H)

N-(3-Methylphenyl)-2-(1-oxopyridin-4-ylmethylthio)pyridine-3-carboxamide(Compound No. 4-3)

¹H-NMR(400MHz,DMSO-d₆)

δ2.30(s,3H),4.38(s,2H),6.93(d,J=7.6Hz,1H),7.20-7.31(m,2H),7.41(d,J=7.1Hz,2H),7.44(m,1H),7.55(s,1H),7.95(dd,J=7.6,1.7 Hz,1H),8.09(d,J=7.1Hz,2H),8.59(dd,J=4.9,1.7 Hz,1H),10.38(s,1H)

N-(3,5-Dimethylphenyl)-2-(1-oxopyridin-4-ylmethylthio)pyridine-3-carboxamide(Compound No. 4-4)

¹H-NMR(400MHz,DMSO-d₆)

δ2.25(s,6H),4.38(s,2H),6.76(s,1H),7.27-7.34(m,3H),7.40-7.42(m,2H),7.93(dd,J=7.6,1.7Hz,1H),8.09(dd,J=5.1,2.0 Hz,2H),8.58(dd,J=4.7,1.7 Hz,1H),10.30(s,1H)

N-(3,4-Dimethylphenyl)-2-(1-oxopyridin-4-ylmethylthio)pyridine-3-carboxamide(Compound No. 4-5)

¹H-NMR(500MHz,DMSO-d₆)

δ 2.19(s,3H),2.21(s,3H),4.37(s,2H),7.09(d,J=8.2 Hz,1H),7.28(dd,J=7.6,4.9Hz,1H) ,7.38(s,1H),7.41(dd,J=7.3,2.0 Hz,2H),7.48(s,1H),7.94(dd,J=7.6,1.5Hz,1H),8.09(dd,J=4.9,2.0 Hz,2H),8.58(dd,J=4.9,1.5 Hz,1H),10.29(s,1H)

N-(3-Isopropylphenyl)-2-(1-oxopyridin-4-ylmethylthio)pyridine-3-carboxamide(Compound No. 4-6)

¹H-NMR(500MHz,DMSO-d₆)

δ 1.20(d,J=6.7 Hz,6H),2.87(m,1H),4.38(s,2H),7.00(d,J=7.6Hz,1H),7.24-7.31(m,2H),7.41(d,J=7.0 Hz,2H),7.51(d,J=7.6Hz,1H),7.59(s,1H),7.96(dd,J=7.7,1.5 Hz,1H),8.09(d,J=7.0Hz,2H),8.59(dd,J=4.8,1.5 Hz,1H), 10.39(s,1H)

N-(4-Fluoro-3-methylphenyl)-2-(1-oxopyridin-4-ylmethylthio)pyridine-3-carboxamide(Compound No. 4-7)

¹H-NMR(500MHz,DMSO-d₆)

δ 2.23(s,3H),4.38(s,2H),7.12(d,J=9.2 Hz,1H),7.30(dd,J=7.7,4.9 Hz,1H),7.41(dd,J=5.2,1.8 Hz,2H),7.48(m,1H),7.63(m,1H),7.95(dd,J=7.7,1.5Hz,1H),8.09(dd,J=5.2,2.7 Hz,2H),8.59(dd,J=4.9,1.5 Hz,1H),10.43(s,1H)

N-(5-Indanyl)-2-(1-oxopyridin-4-ylmethylthio)pyridine-3-carboxamide(Compound No. 4-8)

¹H-NMR(500MHz,DMSO-d₆)

δ 1.98-2.03(m,2H),2.80-2.89(m,4H),4.37(s,2H),7.18(d,J=7.9Hz,1H),7.29(dd,J=7.6, 4.9 Hz,1H),7.39(m,1H),7.41(d,J=7.3Hz,2H),7.61(s,1H),7.93(dd,J=7.6,1.5 Hz,1H), 8.09(dd,J=5.2,2.1Hz,2H),8.58(dd,J=4.9,1.5 Hz,1H),10.30(s,1H)

2-(1-Oxopyridin-4-ylmethylthio)-N-(4-trifluoromethoxyphenyl)pyridine-3-carboxamide(Compound No. 4-9)

¹H-NMR(500MHz,DMSO-d₆)

δ 4.39(s,2H),7.31(dd,J=7.6,4.9 Hz,1H),7.36-7.38(m,2H),7.41(d,J=7.0Hz,2H),7.79-7.81(m,2H),7.99(dd,J=7.6,1.8 Hz,1H),8.09(d,J=7.0Hz,2H),8.60(dd,J=4.9,1.8 Hz,1H),10.66(s,1H)

N-(4-tert-Butylphenyl)-2-(1-oxopyridin-4-ylmethylthio)pyridine-3-carboxamide(Compound No. 4-10)

¹H-NMR(500MHz,DMSO-d₆)

δ 1.27(s,9H),4.38(s,2H),7.29(dd,J=7.6,4.9 Hz,1H),7.36(dd,J=6.8,2.0Hz,2H),7.41(dd,J=5.2,2.1 Hz,2H),7.60(d,J=8.8 Hz,2H),7.94(dd,J=7.6,1.5Hz,1H),8.09(dd,J=5.2,2.1 Hz,2H),8.58(dd,J=4.9,1.5 Hz,1H),10.38(s,1H)

N-(3-Chloro-4-trifluoromethoxyphenyl)-2-(1-oxopyridin-4-ylmethylthio)-pyridine-3-carboxamide(Compound No. 4-11)

¹H-NMR(500MHz, CDCl₃)

δ 4.40(s,2H),7.15(dd,J=7.6,4.8 Hz,1H),7.31(d,J=7.0Hz,2H),7.56(dd,J=8.1,2.6 Hz,1H),7.91(dd,J=7.6,1.8Hz,1H),7.92-7.98(m,4H),8.52(dd,J=4.8,1.8 Hz,1H),8.63(s,1H)

Example 5N-(4-Chlorophenyl)-2-[1-(4-pyridyl)ethylthio]pyridine-3-carboxamide(Compound No. 5-1)

N,N-Diisopropylethylamine (0.29 mL, 1.7 mmol) andO-(7-azabenzotriazol-1-yl)-N,N,N′, N′-tetramethyluroniumhexafluorophosphate (330 mg, 0.87 mmol) were added to a solution of2-[1-(4-pyridyl)ethylthio]pyridine-3-carboxylic acid (200 mg, 0.77 mmol,Reference compound No. 5-1) and 4-chloroaniline (110 mg, 0.85 mmol) inN,N-dimethylformamide (2.0 mL), then the mixture was stirred at roomtemperature for 13 hours. Ethyl acetate (30 mL) was added to thereaction mixture, the ethyl acetate layer was washed with a saturatedaqueous sodium hydrogencarbonate solution (30 mL) twice and brine (30mL) twice, then dried over anhydrous magnesium sulfate. The resultingresidue by evaporated under reduced pressure was purified by silica gelcolumn chromatography to give 41 mg of the target compound as acolorless solid. (Yield 14%)

¹H-NMR(500MHz,DMSO-d₆)

δ 1.63(d,J=7.1 Hz,3H),5.16(q,J=7.1 Hz,1H),7.27(dd,J=7.6,4.6Hz,1H),7.40-7.43(m,2H),7.46(dd,J=4.4,1.5 Hz,2H),7.72(d,J=8.5Hz,2H),7.93(dd,J=7.6,1.8 Hz,1H),8.47(dd,J=4.4,1.5Hz,2H),8.57(dd,J=4.6,1.8 Hz,1H),10.60(s,1H)

Below compound (No. 5-2) was obtained by a method similar to Example 5.

N-(3-Chlorophenyl)-2-[1-(4-pyridyl)ethylthio]pyridine-3-carboxamide(Compound No. 5-2)

¹H-NMR(400MHz,DMSO-d₆)

δ 1.63(d,J=7.3 Hz,3H),5.16(q,J=7.3 Hz,1H),7.18(ddd,J=8.1,2.1,0.9Hz,1H),7.28(dd,J=7.8,4.9 Hz,1H),7.39(m,1H),7.46(dd,J=4.4,1.5Hz,2H),7.57(d,J=8.0 Hz,1H),7.89(m,1H),7.94(dd,J=7.8,1.7Hz,1H),8.47(dd,J=4.4,1.5 Hz,2H),8.58(dd,J=4.9,1.7 Hz,1H),10.60(s,1H)

Example 62-(2-Carboxypyridin-4-ylmethylthio)-N-(3,5-dimethylphenyl)pyridine-3-carboxamide(Compound No. 6-1)

A 1N aqueous sodium hydroxide solution (0.5 mL) was added to a solutionofN-(3,5-dimethylphenyl)-2-(2-ethoxycarbonylpyridin-4-ylmethylthio)pyridine-3-carboxamide(95 mg, 0.22 mmol, Compound No. 1-241) in methanol (2 mL), then themixture was stirred at room temperature for 1.5 hours. 1N hydrochloricacid (1 mL) was added to the reaction mixture, and this mixture wasdiluted with ethyl acetate (35 mL). The mixture was washed with brine(20 mL), and then the organic layer was dried over anhydrous magnesiumsulfate. The solvent was evaporated under reduced pressure, then theresulting residue was filtered off. The solid was washed with diethylether, and then dried at 50° C. under reduced pressure to give 74 mg ofthe target compound as an orange solid. (Yield 84%)

¹H-NMR(500MHz,DMSO-d₆)

δ 2.25(s,6H),4.50(s,2H),6.76(s,1H),7.28(dd,J=7.8,5.0 Hz,1H),7.32(s,2H),7.64(dd,J=4.9,1.5 Hz,1H),7.94(dd,J=7.8,1.8 Hz,1H),8.09(d,J=0.9 Hz,1H),8.56-8.59(m,2H),10.31(s,1H),12.50-13.50(br s, 1H)

Example 7N-(3,5-Dimethylphenyl)-2(2-n-propylaminocarbonylpyridin-4-yl-methylthio)pyridine3 carboxamide (Compound No. 7-1)

N,N-Diisopropylethylamine (40 μL, 0.23 mmol) andO-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (51 mg, 0.14 mmol) were added to a solution of2-(2-carboxypyridine-4-ylmethylthio)-N-(3,5-dimethylphenyl)pyridine-3-carboxamide(42 mg, 0.11 mmol, Compound No. 6-1) and n-propylamine (34 μL, 0.41mmol) in N,N-dimethylformamide (1 mL) at room temperature, this mixturewas stirred at 40° C. for 3 hours. The reaction mixture was diluted withethyl acetate (20 mL), then the ethyl acetate layer was washed with asaturated aqueous sodium hydrogencarbonate solution (40 mL) and brine(30 mL) and dried over anhydrous magnesium sulfate. The solvent wasevaporated under reduced pressure, and the resulting residue was washedwith diethyl ether. This solid was dried at 50° C. under reducedpressure to give 21 mg of the target compound as a white solid. (Yield46%)

¹H-NMR(500MHz,DMSO-d₆)

δ 0.85(t,J=7.3Hz,3H),1.48-1.56(m,2H),2.25(s,6H),3.20-3.25(m,2H),4.50(s,2H),6.76(s,1H),7.28(dd,J=7.3,4.9Hz,1H),7.32(s,2H),7.60(dd,J=4.9,1.8 Hz,1H),7.93(dd,J=7.3,1.7Hz,1H),8.06(d,J=0.9 Hz,1H),8.51(d,J=4.9 Hz,1H),8.56(dd,J=4.9,1.7Hz,1H),8.71(t,J=5.1 Hz,1H),10.31(s,1H)

Below compounds (No. 7-2˜4) were obtained by a method similar to Example7.

2-[2-(4-Chlorophenylaminocarbonyl)pyridin-4-ylmethylthio]-N-(3,5-dimethylphenyl)pyridine-3-carboxamide(Compound No. 7-2)

¹H-NMR(500MHz,DMSO-d₆)

δ 2.25(s,6H),4.55(s,2H),6.76(s,1H),7.29(dd,J=7.6,4.9 Hz,1H),7.32(s,2H),7.39-7.43(m,2H),7.70(dd,J=4.9,1.8Hz,1H),7.92-7.96(m,3H),8.20(d,J=1.2Hz,1H),8.58(dd,J=4.9,1.8Hz,1H),8.62(d,J=5.2 Hz,1H),10.32(s,1H),10.75(s,1H)

N-(3,5-Dimethylphenyl)-2-(2-methylaminocarbonylpyridin-4-ylmethylthio)pyridine-3-carboxamide(Compound No. 7-3)

¹H-NMR(400MHz,DMSO-d₆)

δ 2.25(s,6H),2.79(d,J=4.9Hz,3H),4.50(s,2H),6.76(s,1H),7.28(dd,J=7.5,4.9Hz,1H),7.32(s,2H),7.59(m,1H),7.94(m,1H),8.06(s,1H),8.50(d,J=5.1Hz,1H),8.56(dd,J=4.9,1.7 Hz,1H),8.71(d,J=4.9 Hz,1H),10.32(s,1H)

N-(3,5-Dimethylphenyl)-2-[2-(2-methoxyethylaminocarbonyl)pyridin-4-ylmethylthio]pyridine-3-carboxamide(Compound No. 7-4)

¹H-NMR(400MHz,DMSO-d₆)

δ2.25(s,6H),3.25(s,3H),3.44-3.45(m,4H),4.51(s,2H),6.76(s,1H),7.28(dd,J=7.6,4.9Hz,1H),7.32(s,2H),7.61(d,J=4.9 Hz,1H),7.93(d,J=7.6Hz,1H),8.07(s,1H),8.51(d,J=5.1 Hz,1H),8.56(dd,J=4.9,1.7Hz,1H),8.64(s,1H),10.32(s,1H)

Example 82-(2-Carbamoylpyridin-4-ylmethylthio)-N-(3,5-dimethylphenyl)pyridine-3-carboxamide(Compound No. 8-1)

Triphenylphospine (200 mg, 0.76 mmol) and carbon tetrabromide (273 mg,0.82 mmol) were added to a solution of2-carbamoyl-4-(hydroxymethyl)pyridine (101 mg, 0.66 mmol, Referencecompound No. 13-1) in methylene chloride (3 mL), then the mixture wasstirred at room temperature for 3 hours. The solvent of the reactionsolution was evaporated under reduced pressure, and then the resultingresidue was purified by silica gel column chromatography to give4-bromomethyl-2-carbamoylpyridine. Triethylamine (134 μL, 0.96 mmol) wasadded dropwise to a solution of this bromo-intermediate andN-(3,5-dimethylphenyl)-2-thiopyridone-3-carboxamide (103 mg, 0.40 mmol,Reference compound No. 18-1) in N,N-dimethylformamide (1 mL) at roomtemperature, then the mixture was stirred for 15 hours. The reactionmixture was diluted with ethyl acetate (50 mL), then the ethyl acetatelayer was washed with a saturated aqueous sodium hydrogencarbonatesolution (100 mL) and brine (50 mL), and then dried over anhydrousmagnesium sulfate. The solvent was evaporated under reduced pressure,and then the resulting residue was purified by silica gel columnchromatography to give 40 mg of the target compound as a white solid.(Yield 16%)

¹H-NMR(500MHz,DMSO-d₆)

δ 2.25(s,6H),4.50(s,2H),6.76(s,1H),7.28(dd,J=7.6,4.9 Hz,1H),7.32(s,2H),7.59-7.61(m, 2H),7.93(dd,J=7.6,1.8 Hz,1H),8.05(s,1H),8.07(d,J=0.9Hz,1H),8.51(d,J=5.2 Hz, 1H),8.56(dd,J=4.9,1.8 Hz,1H),10.32(s,1H)

Example 9N-(3,5-Dimethylphenyl)-1-methyl-5-(4-pyridylmethylthio)pyrazole-4-carboxamide(Compound No. 9-1)

4-(4-Formyl-3-methoxyphenoxy)butyrylaminomethylpolystyrene (100 mg,0.055 mmol) was swollen with a solution of ethyl orthoformate (3.0 mL)in anhydrous N,N-dimethylformamide (3.0 mL). 3,5-Dimethylaniline (130mg, 1.1 mmol) and acetic acid (0.033 mL) were added thereto, then thewhole was shaken at room temperature for 14 hours. Sodiumtriacetoxyborohydride (63 mg, 0.29 mmol) was added to the reactionmixture, then this reaction mixture was shaken at room temperature for14 hours. The reaction mixture was filtered, and then this polystyreneresin was washed with methanol (6.0 mL) and then with chloroform (6.0mL) three times alternately. The resin was washed with diethyl ether(6.0 mL), and dried under reduced pressure to give amine-derivativepolystyrene (I).

On the other hand, 5-iodo-1-methylpyrazole-4-carboxylic acid (150 mg,0.58 mmol), given by hydrolysis of 5-iodo-1-methylpyrazole-4-carboxylicacid ethyl ester (Reference compound No. 15-2), and oxalyl chloride(0.053 mL, 0.61 mmol) were stirred at 50° C. for 1 hour.N,N-Diisopropylethylamine (0.51 mL, 2.9 mmol) and amine-derivativepolystyrene(I) were added to a solution of5-iodo-1-methylpyrazole-4-carbonyl chloride prepared by an above methodin anhydrous methylene chloride (3.3 mL), and then the whole was shakenat room temperature for 19 hours. The reaction mixture was filtered, thepolystyrene resin was washed with methanol (6.0 mL) and chloroform (6.0mL) four times alternately, and then the resin was washed with diethylether (6.0 mL), and dried under reduced pressure to giveamide-derivative polystyrene (II). This resin(II),tris(dibenzylideneacetone)dipalladium(0) (160 mg, 0.17 mmol),1,1-bis(diphenylphosphino)ferrocene (400 mg, 0.73 mmol), andN,N-diisopropylethylamine (0.60 mL, 3.3 mmol) were suspended inN,N-dimethylacetamide (5.0 mL). This suspension was frozen, allowed tostand under reduced pressure, and melted. This procedure was repeatedtwice and dissolved oxygen in the solvent was removed,4-pyridinemethanethiol hydrochloride (0.40 g, 2.70 mmol) was addedthereto, and then the reaction mixture was stirred at 60° C. under anargon atmosphere for 24 hours. The reaction mixture was filtered, theresulting resin was washed with N,N-dimethylformamide (6.0 mL) twice,with methanol (6.0 mL) and chloroform (6.0 mL) three times alternately,and with diethyl ether (6.0 mL), then dried under reduced pressure. Asolution of 20% trifluoroacetic acid in methylene chloride (5.0 mL) wasadded to this resin, the whole was shaken at room temperature for 30minutes, and then polystylene resin was filtered out. The filtrate wasdiluted with methylene chloride (4.0 mL), and then a saturated aqueoussodium hydrogencarbonate solution was added to adjust to pH 7. Themethylene chloride layer was evaporated under reduced pressure, and thenthe resulting residue was purified by silica gel column chromatographyto give 7.0 mg of the title compound as a yellow solid. (Yield 36%)

¹H-NMR(500MHz, CDCl₃)

δ 2.33(s,6H),3.59(s,3H),3.97(s,2H),6.80(s,1H),6.94(dd,J=4.4,1.6 Hz,2H),7.22(s,2H),8.11(s,1H),8.48(dd,J=4.4,1.6 Hz,2H),8.81(s,1H)

Below compounds (No. 9-2-47) were obtained by a method similar toExample 9.

N-(5-Indanyl)-1-methyl-5-(4-pyridylmethylthio)pyrazole-4-carboxamide(Compound No. 9-2)

¹H-NMR(500MHz, CDCl₃)

δ 2.08-2.11(m,2H),2.88-2.95(m,4H),3.60(s,3H),3.97(s,2H),6.94(d,J=5.7Hz,2H),7.19(d,J=7.9 Hz,1H),7.26(m,1H),7.54(s,1H),8.11(s,1H),8.48(d,J=5.7Hz,2H),8.83(s,1H)

N-(4-Chloro-3-methylphenyl)-1-methyl-5-(4-pyridylmethylthio)pyrazole-4-carboxamide(Compound No. 9-3)

¹H-NMR(500MHz, CDCl₃)

δ 2.39(s,3H),3.63(s,3H),3.96(s,2H),6.93(dd,J=4.6,1.5Hz,2H),7.30(d,J=8.6Hz,1H), 7.34(dd,J=8.6,2.5 Hz,1H),7.48(d,J=2.5Hz,1H),8.11(s,1H),8.47(dd,J=4.6,1.5 Hz, 2H),8.82(s,1H)

1-Methyl-5-(4-pyridylmethylthio)-N-(4-trifluoromethoxyphenyl)pyrazole-4-carboxamide(Compound No. 9-4)

¹H-NMR(400MHz, CDCl₃)

δ 3.67(s,3H),3.96(s,2H),6.92(dd,J=4.4,1.6 Hz,2H),7.61(d,J=8.2 Hz,2H),7.70(d,J=8.2 Hz,2H),8.15(s,1H),8.46(dd,J=4.4,1.6 Hz,2H),9.04(s,1H)

1-Methyl-5-(4-pyridylmethylthio)-N-(4-trifluoromethylphenyl)pyrazole-4-carboxamide(Compound No. 9-5)

¹H-NMR(500MHz, CDCl₃)

δ 3.64(s,3H),3.96(s,2H),6.91-6.92(m,2H),7.21(d,J=8.9Hz,2H),7.60(d,J=8.9Hz,2H),8.13(s,1H),8.45-8.47(m,2H),8.98(s,1H)

N-(4-IsopropoxyphenyD-1-methyl-5-(4-pyridylmethylthio)pyrazole-4-carboxamide(Compound No. 9-6)

¹H-NMR(500MHz, CDCl₃)

δ 1.34(d,J=6.1Hz,6H),3.61(s,3H),3.96(s,2H),4.54(m,1H),6.89(dt,J=9.8,2.8Hz,2H),6.93(dd,J=4.4,1.5Hz,2H),7.46(dt,J=9.8,2.8 Hz,2H),8.11(s,1H),8.47(dd,J=4.4,1.5Hz,2H),8.74(s,1H)

N-(5-Indanyl)-2-(4-pyridylmethylthio)-4,5,6,7-tetrahydrobenzothiophene-3-carboxamide(Compound No. 9-7)

¹H-NMR(500MHz, CDCl₃)

δ 1.74-1.84(m,4H),2.06-2.12(m,2H),2.68(t,J=6.1 Hz,2H),2.78(t,J=6.0Hz,2H),2.88-2.94(m,4H),3.92(s,2H),7.07(dd,J=4.3,1.5Hz,2H),7.20(s,2H),7.55(s,1H),8.17(s,1H),8.46(dd,J=4.3,1.5 Hz,2H)

N-(3,5-Dimethylphenyl)-2-(4-pyridylmethylthio)-4,5,6,7-tetrahydrobenzothiophene-3-carboxamide(Compound No. 9-8)

¹H-NMR(500MHz, CDCl₃)

δ 1.77-1.82(m,4H),2.33(s,6H),2.68(t,J=6.1 Hz,2H),2.79(t,J=6.1Hz,2H),3.92(s,2H),6.80(s,1H),7.07(dd,J=4.5,1.6Hz,2H),7.19(s,2H),8.16(s,1H),8.47(dd,J=4.5,1.6 Hz,2H)

N-(4-Chloro-3-methylphenyl)-2-(4-pyridylmethylthio)-4,5,6,7-tetrahydrobenzothiophene-3-carboxamide(Compound No. 9-9)

¹H-NMR(500MHz, CDCl₃)

δ 1.76-1.84(m,4H),2.39(s,3H),2.70(t,J=6.1 Hz,2H),2.78(t,J=6.1Hz,2H),3.92(s,2H),7.05(dd,J=4.3,1.5Hz,2H),7.27-7.29(m,2H),7.48(s,1H),8.22(s,1H),8.47(dd,J=4.3,1.5 Hz,2H)

2-(4-Pyridylmethylthio)-N-(4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydrobenzothiophene-3-carboxamide(Compound No. 9-10)

¹H-NMR(500MHz, CDCl₃)

δ 1.77-1.86(m,4H),2.71(t,J=6.2 Hz,2H),2.79(t,J=6.2Hz,2H),3.92(s,2H),7.03(dd,J=4.3,1.5 Hz,2H),7.61(d,J=8.8Hz,2H),7.66(d,J=8.8 Hz,2H),8.46(dd,J=4.3,1.5 Hz,2H),8.49(s,1H)

2-(4-Pyridylmethylthio)-N-(4-trifluoromethylphenyl)-4,5,6,7-tetrahydrobenzothiophene-3-carboxamide(Compound No. 9-11)

¹H-NMR(500MHz, CDCl₃)

δ 1.75-1.84(m,4H),2.70(t,J=6.3 Hz,2H),2.78(t,J=6.1Hz,2H),3.92(s,2H),7.04(dd,J=4.6,1.5 Hz,2H),7.21(d,J=8.6Hz,2H),7.57(d,J=8.6 Hz,2H),8.30(br s, 1H),8.46(dd,J=4.6,1.5 Hz,2H)

N-(4-Isopropoxyphenyl)-2-(4-pyridylmethylthio)-4,5,6,7-tetrahydrobenzothiophene-3-carboxamide(Compound No. 9-12)

¹H-NMR(500MHz, CDCl₃)

δ 1.34(d,J=6.1 Hz,6H),1.78-1.82(m,4H),2.69(t,J=6.0 Hz,2H),2.78(t,J=6.0Hz,2H),3.92(s,2H),4.53(m,1H),6.89(d,J=8.9Hz,2H),7.07(dd,J=4.4,1.7Hz,2H),7.44(d,J=8.9Hz,2H),8.05(s,1H),8.47(dd,J=4.4,1.7 Hz,2H)

N-(3-Methylphenyl)-5-(4-pyridylmethylthio)furan-2-carboxamide (CompoundNo. 9-13)

¹H-NMR(500MHz, CDCl₃)

δ2.38(s,3H),3.98(s,2H),6.98(m,1H),7.12-7.13(m,3H),7.25-7.26(m,2H),7.41(dd,J=8.2,2.4 Hz,1H),7.48(s,1H),7.79(s,1H),8.57(dd,J=4.3,1.5 Hz,2H)

N-(5-Indanyl)-5-(4-pyridylmethylthio)furan-2-carboxamide (Compound No.9-14)

¹H-NMR(500MHz, CDCl₃)

δ 2.06-2.13(m,2H),2.88-2.95(m,4H),3.98(s,2H),6.48(d,J=3.4Hz,1H),7.12-7.14(m,3H),7.21(d,J=8.1 Hz,1H),7.29(dd,J=8.1,2.0Hz,1H),7.58(s,1H), 7.78(s,1H),8.57(dd,J=4.6,1.8 Hz,2H)

N-(3-Fluoro-4-methylphenyl)-5-(4-pyridylmethylthio)furan-2-carboxamide(Compound No. 9-15)

¹H-NMR(500MHz, CDCl₃)

δ 2.26(d,J=1.8 Hz,3H),3.98(s,2H),6.49(d,J=3.7Hz,1H),7.13-7.16(m,5H),7.54(dd,J=12.2,1.8Hz,1H),7.77(s,1H),8.57(dd,J=4.3,1.5 Hz,2H)

N-(3-Isopropylphenyl)-5-(4-pyridylmethylthio)furan-2-carboxamide(Compound No. 9-16)

¹H-NMR(500MHz, CDCl₃)

δ 1.28(d,J=6.7 Hz,6H),2.94(m,1H),3.99(s,2H),6.48(d,J=3.4Hz,1H),7.04(d,J=7.6 Hz,1H),7.13-7.14(m,3H),7.30(t,J=7.8Hz,1H),7.46(m,1H),7.50(m,1H),7.79(s,1H),8.57(dd,J=4.6,1.5 Hz,2H)

N-(4-Fluoro-3-methylphenyl)-5-(4-pyridylmethylthio)furan-2-carboxamide(Compound No. 9-17)

¹H-NMR(500MHz, CDCl₃)

δ 2.30(d,J=1.8 Hz,3H),3.98(s,2H),6.49(d,J=3.4 Hz,1H),7.00(t,J=8.9Hz,1H),7.13-7.14(m,3H),7.37(m,1H),7.49(dd,J=6.7,2.4Hz,1H),7.71(s,1H),8.57(dd,J=4.6,1.8 Hz,2H)

N-(3-Isoquinolyl)-5-(4-pyridylmethylthio)furan-2-carboxamide (CompoundNo. 9-18)

¹H-NMR(500MHz, CDCl₃)

δ 4.04(s,2H),6.46(d,J=3.4 Hz,1H),7.14(dd,J=4.4,1.6 Hz,2H),7.20(d,J=3.4Hz,1H),7.52(m,1H),7.69(m,1H),7.87(dd,J=8.2,0.9 Hz,1H),7.93(dd,J=8.2,0.9Hz,1H),8.56(dd,J=4.4,1.6 Hz,2H),8.67(s,1H),8.79(s,1H),9.05(s,1H)

N-(3-Chlorophenyl)-5-(4-pyridylmethylthio)furan-2-carboxamide (CompoundNo. 9-19)

¹H-NMR(500MHz, CDCl₃)

δ 3.99(s,2H),6.50(d,J=3.4 Hz,1H),7.13-7.16(m,4H),7.30(t,J=8.1Hz,1H),7.45(ddd,J=8.2,2.1,0.9 Hz,1H),7.78(br s, 1H),7.78(t,J=2.1Hz,1H),8.58(dd,J=4.3,1.5 Hz,2H)

N-(3-Chloro-4-trifluoromethoxyphenyl-5-(4-pyridylmethylthio)furan-2-carboxamide(Compound No. 9-20)

¹H-NMR(500MHz, CDCl₃)

δ 3.99(s,2H),6.52(d,J=3.6 Hz,1H),7.15(dd,J=4.3,1.5 Hz,2H),7.17(d,J=3.6Hz,1H),7.32(m,1H),7.50(dd,J=8.9,2.4 Hz,1H),7.75(br s, 1H),7.92(d,J=2.7Hz,1H),8.58(dd,J=4.3,1.5 Hz,2H)

N-(3-Chloro-4-methylphenyl)-5-(4-pyridylmethylthio)furan-2-carboxamide(Compound No. 9-21)

¹H-NMR(500MHz, CDCl₃)

δ 2.36(s,3H),3.98(s,2H),6.49(d,J=3.4 Hz,1H),7.13-7.14(m,3H),7.21(d,J=8.1Hz,1H),7.38(dd,J=8.1,2.1 Hz,1H),7.73(br s, 1H),7.74(d,J=2.1Hz,1H),8.57(dd,J=4.3,1.5 Hz,2H)

N-(4-tert-Butylphenyl)-5-(4-pyridylmethylthio)furan-2-carboxamide(Compound No. 9-22)

¹H-NMR(500MHz, CDCl₃)

δ 1.33(s,9H),3.98(s,2H),6.49(d,J=3.4 Hz,1H),7.13-7.14(m,3H),7.39(d,J=8.9Hz,2H),7.54(d,J=8.9 Hz,2H),7.74(br s, 1H),8.57(dd,J=4.3,1.5 Hz,2H)

5-(4-Pyridylmethylthio)-N-(6-quinolyl)furan-2-carboxamide (Compound No.9-23)

¹H-NMR(500MHz, CDCl₃)

δ 4.01(s,2H),6.53(d,J=3.4 Hz,1H),7.16(dd,J=4.4,1.7 Hz,2H),7.20(d,J=3.4Hz,1H),7.42(dd,J=8.8,4.3 Hz,1H),7.71(dd,J=8.8,2.4 Hz,1H),8.00(brs,1H),8.12(d,J=9.2 Hz,1H),8.17(m,1H),8.44(d,J=2.4 Hz,1H),8.59(dd,J=4.4,1.7Hz,2H),8.87(dd,J=4.0,1.5 Hz,1H)

N-(4-Bromo-3-methylphenyl)-5-(4-pyridylmethylthio)furan-2-carboxamide(Compound No. 9-24)

¹H-NMR(500MHz, CDCl₃)

δ 2.42(s,3H),3.98(s,2H),6.49(d,J=3.4Hz,1H),7.13-7.14(m,3H),7.33(dd,J=8.6,2.4 Hz,1H),7.51(d,J=8.6Hz,1H),7.56(d,J=2.4 Hz,1H),7.73(br s,1H),8.57(dd,J=4.6,1.8 Hz,2H)

5-(4-Pyridylmethylthio)-N-(4-trifluoromethoxyphenyl)furan-2-carboxamide(Compound No. 9-25)

¹H-NMR(500MHz, CDCl₃)

δ 3.98(s,2H),6.51(d,J=3.5 Hz,1H),7.15(dd,J=4.4,1.5 Hz,2H),7.16(d,J=3.5Hz,1H),7.23(d,J=8.2 Hz,2H),7.66(d,J=0.9 Hz,2H),7.78(br s,1H),8.58(dd,J=4.4,1.5 Hz, 2H)

N-(4-Dimethylaminophenyl)-5-(4-pyridylmethylthio)furan-2-carboxamide(Compound No. 9-26)

¹H-NMR(500MHz, CDCl₃)

δ 2.95(s,6H),3.97(s,2H),6.47(d,J=3.5 Hz,1H),6.74(d,J=9.0Hz,2H),7.09(d,J=3.5 Hz,1H),7.13(dd,J=4.6,1.7 Hz,2H),7.47(d,J=9.0Hz,2H),7.67(br s,1H),8.56(dd,J=4.6,1.7 Hz,2H)

N-(1-Acetyl-2,3-dihydroindol-5-yl)-5-(4-pyridylmethylthio)furan-2-carboxamide(Compound No. 9-27)

¹H-NMR(500MHz, CDCl₃)

δ 2.23(s,3H),3.23(t,J=8.5 Hz,2H),3.98(s,2H),4.09(t,J=8.5Hz,2H),6.47(d,J=3.4 Hz,1H),7.12-7.17(m,4H),7.78(d,J=2.0 Hz,1H),7.83(brs, 1H),8.19(d,J=8.5 Hz,1H),8.56(dd,J=4.4,1.5 Hz,2H)

N-(4-Isopropoxyphenyl)-5-(4-pyridylmethylthio)furan-2-carboxamide(Compound No. 9-28)

¹H-NMR(400MHz, CDCl₃)

δ 1.34(d,J=6.1 Hz,6H),3.97(s,2H),4.52(m,1H),6.48(d,J=3.4Hz,1H),6.89(dd,J=6.6,2.2 Hz,2H),7.10(m,3H),7.51(dd,J=6.6,2.2Hz,2H),7.73(s,1H),8.56(dd,J=4.4,1.7 Hz,2H)

5-(4-Pyridylmethylthio)-N-(4-trifluoromethylthiophenyl)furan-2-carboxamide(Compound No. 9-29)

¹H-NMR(400MHz, CDCl₃)

δ 3.99(s,2H),6.52(d,J=3.4 Hz,1H),7.15(dd,J=4.4,1.7 Hz,2H),7.18(d,J=3.4Hz,1H),7.66(d,J=8.8 Hz,2H),7.71(d,J=8.8Hz,2H),7.84(s,1H),8.58(dd,J=4.4,1.7 Hz,2H)

N-(4-Bromophenyl)-5-(4-pyridylmethylthio)furan-2-carboxamide (CompoundNo. 9-30)

¹H-NMR(400MHz, CDCl₃)

δ 3.98(s,2H),6.50(d,J=3.4 Hz,1H),7.14(dd,J=4.4, 1.7 Hz,2H),7.15(d,J=3.4Hz,1H),7.49(d,J=9.2 Hz,2H),7.54(d,J=9.2 Hz,2H),7.77(br s,1H),8.57(dd,J=4.4,1.5 Hz,2H)

N-(3-Methylphenyl)-5(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 9-31)

¹H-NMR(500MHz, CDCl₃)

δ 2.35(s,3H),3.98(s,2H),6.87(d,J=3.9 Hz,1H),6.97(d,J=7.6Hz,1H),7.13(dd,J=4.3,1.5 Hz,2H),7.23(t,J=7.9Hz,1H),7.35(m,1H),7.39(d,J=3.9Hz,1H),7.43(m,1H),7.60(s,1H),8.53(dd,J=4.3,1.5 Hz,2H)

N-(5-Indanyl)-5-(4-pyridylmethylthio)thiophene-2-carboxamide (CompoundNo. 9-32)

¹H-NMR(500MHz, CDCl₃)

δ 2.07-2.10(m,2H),2.86-2.92(m,4H),3.98(s,2H),6.87(d,J=3.9Hz,1H),7.13(dd,J=4.4, 1.5 Hz,2H),7.18(d,J=8.2 Hz,1H),7.23(dd,J=7.9,2.1Hz,1H),7.38(d,J=3.9 Hz,1H),7.51(s,1H),7.57(br s, 1H),8.53(dd,J=4.4,1.5Hz,2H)

N-(3-Fluoro-4-methylphenyl)-5-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 9-33)

¹H-NMR(500MHz, CDCl₃)

δ 2.24(d,J=1.8 Hz,3H),3.99(s,2H),6.86(d,J=3.9Hz,1H),7.13(m,4H),7.40(d,J=3.9Hz,1H),7.47(m,1H),7.71(s,1H),8.52(dd,J=4.6,1.5 Hz,2H)

N-(3-Isopropylphenyl)-5-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 9-34)

¹H-NMR(500MHz, CDCl₃)

δ 1.25(d,J=7.0 Hz,6H),2.91(m,1H),3.99(s,2H),6.87(d,J=4.0Hz,1H),7.03(d,J=7.8 Hz,1H),7.13(dd,J=4.6,1.5 Hz,2H),7.27(t,J=0.8Hz,1H),7.38(dd,J=2.1,0.9 Hz,1H),7.40(d,J=4.0 Hz,1H),7.46(t,J=2.1Hz,1H),7.62(s,1H),8.53(dd,J=4.6,1.5 Hz,2H)

N-(4-Fluoro-3-methylphenyl)-5-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 9-35)

¹H-NMR(500MHz, CDCl₃)

δ 2.27(d,J=1.8 Hz,3H),3.99(s,2H),6.87(d,J=3.9 Hz,1H),6.98(t,J=8.9Hz,1H),7.13(dd,J=4.5,1.7 Hz,2H),7.31(m,1H),7.39(d,J=3.9Hz,1H),7.44(dd,J=6.6,2.6 Hz,1H),7.56(s,1H),8.53(dd,J=4.5,1.7 Hz,2H)

N-(3-Isoquinolyl)-5-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 9-36)

¹H-NMR(500MHz, CDCl₃)

δ 4.02(s,2H),6.92(d,J=4.0 Hz,1H),7.16(dd,J=4.5,1.5Hz,2H),7.49-7.53(m,2H),7.68(m,1H),7.85(d,J=8.2 Hz,1H),7.92(d,J=7.6Hz,1H),8.45(s,1H),8.54(dd,J=4.5,1.5 Hz,2H),8.64(s,1H),9.00(s,1H)

N-(3-Chlorophenyl)-5-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 9-37)

¹H-NMR(500MHz, CDCl₃)

δ 4.00(s,2H),6.89(d,J=3.9 Hz,1H),7.13(m,1H),7.14(dd,J=4.6,1.5Hz,2H),7.28(t,J=8.1 Hz,1H),7.40(d,J=3.9 Hz,1H),7.43(ddd,J=8.1,2.1, 0.9Hz,1H),7.57(s,1H),7.70(t,J=2.1 Hz,1H),8.53(dd,J=4.6,1.5 Hz,2H)

N-(3-Chloro-4-trifluoromethoxyphenyl)-5-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 9-38)

¹H-NMR(500MHz, CDCl₃)

δ 4.01(s,2H),6.89(d,J=3.9 Hz,1H),7.15(dd,J=4.3,1.5Hz,2H),7.30(m,1H),7.43(d,J=3.9 Hz,1H),7.49(dd,J=8.9,2.4Hz,1H),7.68(s,1H),7.85(d,J=2.7 Hz,1H),8.53(dd,J=4.3,1.5 Hz,2H)

N-(3-Chloro-4-methylphenyl)-5-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 9-39)

¹H-NMR(500MHz, CDCl₃)

δ 2.34(s,3H),3.99(s,2H),6.87(d,J=3.9 Hz,1H),7.13(dd,J=4.6,1.5 Hz,2H),7.18(d,J=8.2 Hz,1H),7.35(dd,J=8.2,2.1 Hz,1H),7.40(d,J=3.9 Hz,1H),7.66(d,J=2.1 Hz,1H),7.70(br s, 1H),8.52(dd,J=4.6,1.5 Hz,2H)

N-(4-tert-Butylphenyl)-5-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 9-40)

¹H-NMR(500MHz, CDCl₃)

δ 1.31(s,9H),3.98(s,2H),6.86(d,J=3.7 Hz,1H),7.13(dd,J=4.4,1.6 Hz,2H),7.37(d,J=8.8 Hz,2H),7.39(d,J=3.7 Hz,1H),7.49(d,J=8.8Hz,2H),7.64(s,1H),8.52(dd,J=4.4, 1.6 Hz,2H)

5-(4-Pyridylmethylthio)-N-(6-quinolyl)thiophene-2-carboxamide (CompoundNo. 9-41)

¹H-NMR(500MHz, CDCl₃)

δ 4.01(s,2H),6.91(d,J=3.9 Hz,1H),7.15(dd,J=4.6,1.5Hz,2H),7.41(dd,J=8.2,4.3 Hz,1H),7.49(d,J=4.0 Hz,1H),7.65(dd,J=8.9,2.4Hz,1H),7.97(s,1H),8.08(d,J=9.2 Hz,1H),8.14(dd,J=8.2,1.5Hz,1H),8.42(d,J=2.4 Hz,1H),8.54(dd,J=4.6,1.5 Hz,2H),8.86(dd,J=4.3, 1.5Hz,1H)

N-(4-Bromo-3-methylphenyl)-5-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 9-42)

¹H-NMR(500MHz, CDCl₃)

δ 2.39(s,3H),3.99(s,2H),6.88(d,J=4.0 Hz,1H),7.13(dd,J=4.6,1.5 Hz,2H),7.28(dd,J=8.6,2.5 Hz,1H),7.39(d,J=4.0 Hz,1H),7.48(d,J=8.6 Hz,1H),7.52(d,J=2.5 Hz,1H),7.58(br s, 1H),8.53(dd,J=4.6,1.5 Hz,2H)

5-(4-Pyridylmethylthio)-N-(4-trifluoromethoxyphenyl)thiophene-2-carboxamide(Compound No. 9-43)

¹H-NMR(500MHz, CDCl₃)

δ 4.00(s,2H),6.88(d,J=4.0 Hz,1H),7.14(dd,J=4.5,1.5 Hz,2H),7.21(d,J=8.6Hz,2H),7.42(d,J=4.0 Hz,1H),7.62(d,J=8.6Hz,2H),7.75(s,1H),8.53(dd,J=4.5,1.5 Hz,2H)

N-(1-Acetyl-2,3-dihydroindol-5-yl)-5-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 9-44)

¹H-NMR(500MHz, CDCl₃)

δ 2.23(s,3H),3.22(t,J=8.6 Hz,2H),3.99(s,2H),4.08(t,J=8.6Hz,2H),6.88(d,J=4.0 Hz,1H),7.06(dd,J=8.6,2.1 Hz,1H),7.13(dd,J=4.6,1.5Hz,2H),7.39(d,J=4.0 Hz,1H),7.56(s,1H),7.76(s,1H),8.16(d,J=8.6Hz,1H),8.53(dd,J=4.6,1.5 Hz,2H)

N-(4-Isopropoxyphenyl)-5-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 9-45)

¹H-NMR(500MHz, CDCl₃)

δ 1.33(d,J=5.8 Hz,6H),3.98(s,2H),4.52(m,1H),6.87(d,J=4.0Hz,1H),6.87(d,J=8.9 Hz,2H),7.13(dd,J=4.3,1.5 Hz,2H),7.38(d,J=4.0Hz,1H),7.45(d,J=8.9 Hz,2H),7.54(br s, 1H),8.52(dd,J=4.3,1.5 Hz,2H)

5-(4-Pyridylmethylthio)-N-(4-trffluoromethylthiophenyl)thiophene-2-carboxamide(Compound No. 9-46)

¹H-NMR(500MHz, CDCl₃)

δ 4.01(s,2H),6.90(d,J=4.0 Hz,1H),7.14(dd,J=4.5,1.5 Hz,2H),7.43(d,J=4.0Hz,1H),7.63-7.68(m,4H),7.70(s,1H),8.53(dd,J=4.5,1.5 Hz,2H)

N-(4-Bromophenyl)-5-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 9-47)

¹H-NMR(500MHz, CDCl₃)

δ 3.99(s,2H),6.87(d,J=3.9 Hz,1H),7.13(dd,J=4.6,1.5 Hz,2H),7.41(d,J=3.9Hz,1H),7.45-7.50(m,4H),7.77(s,1H),8.52(dd,J=4.6,1.5 Hz,2H)

Example 10N-(3,5-Dimethylphenyl)-2-[4-(1-methylpyridinio)methylthio]pyridine-3-carboxamideiodide (Compound No. 10-1)

Methyl iodide (36 μL, 0.57 mmol) was added to a solution ofN-(3,5-dimethylphenyl)-2-(4-pyridylmethylthio)pyridine-3-carboxamide(100 mg, 0.29 mmol, Compound No. 1-106) in acetone (3 mL) at roomtemperature, the whole was stirred under shaded condition for 28 hours.The solvent was evaporated under reduced pressure, and then theresulting residue was purified by silica gel column chromatography togive 80 mg of the target compound as a yellow oil. (Yield 57%)

¹H-NMR(500MHz, CDCl₃)

δ 2.28(s,6H),4.37(s,3H),4.56(s,2H),6.75(s,1H),7.15(dd,J=7.7,4.9 Hz,1H),7.40(s,2H),7.82(dd,J=7.7,1.5 Hz,1H),7.96(d,J=6.1Hz,2H),8.48(dd,J=4.9,1.5 Hz,1H),8.60(d,J=6.1 Hz,2H),8.63(s,1H)

Example 11 N-(3 Fluoro 5trifluoromethylphenyl)-2-(4-pyridylmethylthio)benzamide (Compound No.11-1)

N,N-Diisopropylethylamine (1.5 mL, 8.8 mmol) was added to a suspensionof N-(3-fluoro-5-trifluoromethylphenyl)-2-iodobenzamide (1.00 g, 2.4mmol, Reference compound No. 2-3), bis(dibenzylideneacetone)dipalladium(0.12 g, 0.20 mmol), and 1,1′-bis(diphenylphosphino)ferrocene (0.28 g,0.49 mmol) in N,N-dimethylacetamide (20 mL) at room temperature, thenthe reaction bottle was sealed. The mixture was coagulated with liquidnitrogen, sealed under reduced pressure, allowed to stand to roomtemperature, and then the dissolved oxygen was removed (the operation ofdegasification). The operation of degasification was conducted further,and then the reaction mixture was stirred at 60° C. under an argonatmosphere for 19 hours. The reaction mixture was allowed to stand,diluted with ethyl acetate (70 mL), then filterated through celite. Thefiltrate was washed with brine (70 mL) twice, dried over anhydrousmagnesium sulfate, then evaporated under reduced pressure. The resultingresidue was purified by silica gel column chromatography to give 0.29 gof the target compound as a colorless solid. (Yield 29%)

¹H-NMR(500MHz,DMSO-d₆)

δ 4.27(s,2H),7.32(m,1H),7.35(d,J=6.1 Hz,2H),7.41(d,J=8.2Hz,1H),7.46(m,1H),7.50(d,J=8.2 Hz,1H),7.58(d,J=7.3 Hz,1H),7.88(d,J=11.0Hz,1H),7.98(s,1H),8.45(d,J=6.1 Hz,2H),10.87(s,1H)

Below compounds (No. 11-2˜5) were obtained by a method similar toExample 11.

N-(4-Chlorophenyl)-5-(4-pyridylmethylthio)furan-2-carboxamide (CompoundNo. 11-2)

¹H-NMR(400MHz,DMSO-d₆)

δ 4.25(s,2H),6.63(d,J=3.7 Hz,1H),7.24(dd,J=4.4,1.7 Hz,2H),7.28(d,J=3.7Hz,1H),7.41(d,J=9.0 Hz,2H),7.77(d,J=9.0 Hz,2H),8.48(dd,J=4.4,1.7Hz,2H),10.26(s,1H)

N-(4-Chlorophenyl)-5-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 11-3)

¹H-NMR(400MHz,DMSO-d₆)

δ 4.23(s,2H),7.13(d,J=3.9 Hz,1H),7.28(dd,J=4.4,1.7 Hz,2H),7.40(d,J=9.0Hz,2H),7.72(d,J=9.0 Hz,2H),7.85(d,J=3.9 Hz,1H),8.49(dd,J=4.4,1.7Hz,2H),10.31(s,1H)

N-(3,5-Dimethylphenyl)-5-(4-pyridylmethylthio)furan-2-carboxamide(Compound No. 11-4)

¹H-NMR(500MHz,DMSO-d₆)

δ 2.26(s,6H),4.25(s,2H),6.61(d,J=3.4 Hz,1H),6.76(s,1H),7.23(dd,J=4.3,1.5Hz,2H),7.24(d,J=3.4 Hz,1H),7.36(s,2H),8.48(dd,J=4.3,1.5 Hz,2H),9.94(s,1H)

N-(3,5-Dimethylphenyl)-5-(4-pyridylmethylthio)thiophene-2-carboxamide(Compound No. 11-5)

¹H-NMR(500MHz, CDCl₃)

δ 2.31(s,6H),3.98(s,2H),6.79(s,1H),6.86(d,J=4.0 Hz,1H),7.13(dd,J=4.6,1.8Hz,2H),7.21(s,2H),7.38(d,J=4.0 Hz,1H),7.55(br s, 1H),8.52(dd,J=4.6,1.8Hz,2H)

Formulation Examples

Typical formulation examples of the present compound are shown below.

1) Tablet in 100 mg Present compound 1 mg Lactose 66.4 mg Cornstarch 20mg Calcium carboxymethylcellulose 6 mg Hydroxypropylcellulose 4 mgMagnesium stearate 0.6 mg

Tablets according to the above-mentioned formulation are coated with 2mg/tablet of a coating agent, which is a conventional coating agent suchas hydroxypropylmethylcellulose, macrogol or silicone resin, to obtaindesired coated tablets. Desired tablets can be obtained by changingappropriately the kinds and the amounts of the present compound and theadditives.

2) Capsule in 150 mg Present compound  5 mg Lactose 145 mg

Desired capsules can be obtained by changing appropriately the mixingratio of the present compound to lactose.

3) Ophthalmic solution in 100 ml Present compound 100 mg Sodium chloride900 mg Polysorbate 80 200 mg Sodium hydroxide quantum sufficientHydrochloric acid quantum sufficient Sterile purified water quantumsufficient

Desired ophthalmic solutions can be obtained by changing appropriatelythe kinds and the amounts of the present compound and the additives.

Pharmacological Tests

1. Evaluation Tests of Angiogenesis Inhibitory Effects

As one of widely-used methods of evaluating angiogenesis inhibitoryeffects of drugs, a cell growth inhibitory action test using aVEGF-induced HUVEC growth reaction evaluation system was reported inCancer Res., 59, 99-106(1999). According to the method described in theabove-mentioned literature, cell growth inhibitory action tests of thepresent compounds were carried out, their cell growth inhibition rateswere calculated, and angiogenesis inhibitory effects of the presentcompounds were evaluated using the obtained rates as indexes.

Preparation of Test Compound Solutions

Each test compound was dissolved in dimethyl sulfoxide (hereinafterabbreviated as “DMSO”), and the obtained solution was diluted withcommercially available phosphoric acid buffer solution (hereinafterabbreviated as “PBS”) to prepare a 20 μg/ml test compound solution.

Preparation of HUVEC Suspension

HUVEC was suspended in a 0.5% fetal bovine serum (hereinafterabbreviated as “FBS”)-containing F12K medium to prepare a 2×10⁴ cells/mlHUVEC suspension.

Preparation of VEGF Solution

VEGF was dissolved in 0.1% bovine serum albumin-containing PBS, and theobtained solution was diluted with the 0.5% FBS-containing F12K mediumto prepare a 400 ng/ml VEGF solution.

Method of Test and Method of Measurement

-   1) The HUVEC suspension was inoculated in each amount of 100 μl into    each well of a 96-well plate coated with I type collagen (2×10³    cells per well).-   2) One day after inoculation, the test compound solution was added    in an amount of 5 μl per well.-   3) One hour after adding the test compound solution, the VEGF    solution was added in an amount of 5 μl per well.-   4) Three days after adding the VEGF solution, cell counting    kit-8(Dojin Chemical Co., Ltd.) was added in an amount of 10 μl per    well.-   5) After three hours, the above-mentioned plate was attached to an    absorptiometer (multi label counter ARVO), and absorbance at 450 nm    of each well suspension (hereinafter referred to as “test compound    suspension”) was measured.-   6) A test was carried out in the same manner as in 1) to 5) except    that 1.0% DMSO was used instead of the test compound solution. Its    result was used as a control.

Incubation was carried out under conditions of 37° C., 5% carbon dioxideand 95% air in an incubator throughout the above-mentioned test steps.

Calculation of Cell Growth Inhibition Rates

Cell growth inhibition rates, which are indexes of angiogenesisinhibitory effects, were calculated by the following calculationequation.

Calculation EquationCell growth inhibition rate (%)=100−{(Absorbance of test compoundsuspension-A)/(absorbance of control-A)}×100A: Absorbance of only cell suspension (cell+medium)Test Results and Discussion

As examples of test results, Table 1 shows cell growth inhibition rates(%) of test compounds (Compound Nos. 1-1, 1-20, 1-21, 1-22, 1-23, 1-30,1-35, 1-38, 1-42, 1-47, 1-48, 1-49, 1-50, 1-51, 1-54, 1-55, 1-61, 1-64,1-65, 1-69, 1-70, 1-72, 1-74, 1-75, 1-77, 1-78, 1-79, 1-80, 1-83, 1-84,1-85, 1-87, 1-90, 1-91, 1-92, 1-93, 1-95, 1-96, 1-99, 1-102, 1-104,1-106, 1-111, 1-136, 1-137, 1-158, 1-175, 1-209, 1-213, 1-214, 1-215,1-216, 1-226, 1-227, 1-228, 1-230, 1-231, 1-232, 1-236, 1-241, 1-246,1-248, 1-249, 1-250, 1-251, 1-252, 1-253, 1-255, 1-256, 1-263, 1-269,1-270, 1-273, 1-274, 1-275, 1-276, 1-283, 1-284, 1-285, 1-287, 1-289,1-290, 1-291, 1-292, 1-296, 1-300, 1-307, 1-308, 4-1, 4-3, 4-4, 4-5,4-6, 4-7, 4-8, 4-9, 4-10, 4-11, 5-2, 6-1, 7-1, 7-2, 7-3, 7-4 and 8-1).

TABLE 1 Cell growth inhibition Compound rate (%) 1-1 100 1-20 100 1-2199 1-22 100 1-23 100 1-30 100 1-35 100 1-38 100 1-42 94 1-47 100 1-48100 1-49 100 1-50 94 1-51 98 1-54 100 1-55 100 1-61 65 1-64 100 1-65 1001-69 95 1-70 58 1-72 100 1-74 100 1-75 100 1-77 100 1-78 100 1-79 1001-80 100 1-83 100 1-84 100 1-85 95 1-87 100 1-90 100 1-91 100 1-92 1001-93 72 1-95 100 1-96 70 1-99 100 1-102 55 1-104 100 1-106 100 1-111 1001-136 100 1-137 100 1-158 100 1-175 100 1-209 99 1-213 100 1-214 921-215 100 1-216 100 1-226 100 1-227 60 1-228 100 1-230 100 1-231 1001-232 75 1-236 100 1-241 96 1-246 76 1-248 75 1-249 100 1-250 86 1-25177 1-252 100 1-253 100 1-255 85 1-256 100 1-263 100 1-269 53 1-270 991-273 100 1-274 95 1-275 100 1-276 100 1-283 100 1-284 100 1-285 1001-287 95 1-289 100 1-290 100 1-291 100 1-292 100 1-296 100 1-300 1001-307 100 1-308 92 4-1 93 4-3 100 4-4 100 4-5 100 4-6 100 4-7 100 4-8 984-9 100 4-10 100 4-11 100 5-2 96 6-1 72 7-1 100 7-2 100 7-3 100 7-4 1008-1 100

As shown in Table 1, the present compounds demonstrated excellent cellgrowth inhibitory actions. Accordingly, the present compounds haveexcellent angiogenesis inhibitory effects.

2. Evaluation Tests of Anticancer Effects

As one of widely-used methods of evaluating anticancer effects of drugs,a tumor growth inhibitory action test using mouse cancer models wasreported in Cancer Res., 59, 5209-5218(1999). According to the methoddescribed in the above-mentioned literature, tumor growth inhibitoryaction tests of the present compounds were carried out, their tumortissue weight inhibition rates were calculated, and anticancer effectsof the present compounds were evaluated using the obtained rates asindexes.

Preparation of Test Compound Suspension

A 1% aqueous methyl cellulose solution was added to each test compoundto suspend it with a sonicator thereby to prepare a 10 mg/ml testcompound suspension.

Preparation of B16 Cell Suspension

Physiological saline was added to B16 cells to prepare a 3.3×10⁷cells/ml B16 cell suspension.

Method of Test and Method of Measurement

-   1) The back of each mouse (female, six weeks old, C57BL/6 mouse) was    depilated using a depilatory under Nembutal anesthesia.-   2) Several days after depilation, the B16 cell suspension (300 μl)    was injected intradermally into the back of the mouse under Nembutal    anesthesia.-   3) From the B16 cell injection day (i.e. zero day) to tenth day, the    test compound suspension (100 mg/kg/day) was administered orally    once a day every day.-   4) Ten days after injection of the cells, the mouse was euthanized    with a CO₂ gas.-   5) A tumor tissue was extirpated from the mouse, and weight of the    tumor tissue was measured with an electronic balance.-   6) A test was carried out in the same manner as in 1) to 5) except    that the 1% aqueous methyl cellulose solution was used instead of    the test compound suspension, and its result was used as a control.    Calculation of Tumor Tissue Weight Inhibition Rate

Tumor tissue weight inhibition rates (the average of nine mice pergroup), which are indexes of anticancer effects were calculated, fromthe following calculation equation.

Calculation EquationTumor tissue weight inhibition rate (%)=100−(Mx/Mo)×100

-   Mo: Tumor tissue weight of control group-   Mx: Tumor tissue weight of test compound solution administration    group    Test Results and Discussion

As examples of test results, Table 2 shows tumor tissue weightinhibition rates of test compound (Compound Nos. 1-21, 1-22, 1-23, 1-38,1-48, 1-51, 1-54, 1-80, 1-99, 1-104, 1-106, 1-136, 1-137, 1-158, 1-230,1-296, 4-4, 4-8, 4-9 and 4-11).

TABLE 2 Tumor tissue weight Compound inhibition rate (%) 1-21 65 1-22 451-23 57 1-38 43 1-48 73 1-51 59 1-54 69 1-80 66 1-99 64 1-104 49 1-10671 1-136 53 1-137 66 1-158 76 1-230 66 1-296 71 4-4 77 4-8 80 4-9 774-11 62

As shown in Table 2, the present compounds demonstrated excellent tumorgrowth inhibitory actions. Accordingly, the present compounds haveexcellent anticancer effects.

3. Evaluation Tests of Antiarthritic Effects

As one of widely-used methods of evaluating antiarthritic effects ofdrugs, a paw edema inhibitory action test using rat adjuvant arthritismodels is known. Paw edema inhibitory action tests of the presentcompounds were carried out, their paw edema inhibition rates werecalculated, and antiarthritic effects of the present compounds wereevaluated using the obtained rates as indexes.

Preparation of Test Compound Suspension

A 1% aqueous methyl cellulose solution was added to each test compoundto suspend it thereby to prepare a 2 mg/ml test compound suspension.

Preparation of Adjuvant

Liquid paraffin was added to Mycobacterium-butyricum to suspend it toprepare 6 mg/ml adjuvant.

Experimental Method

-   1) The adjuvant (0.1 ml) was injected subcutaneously into a left    hind paw sole of each rat (male, nine weeks old, Lewis rat) to    induce arthritis.-   2) From the adjuvant injection day (i.e. zero day) to 20th day, the    test compound suspension (10 mg/kg/day) was administered orally once    a day every day consecutively.-   3) On the adjuvant injection day, after one day, four days, seven    days, 11 days, 14 days, 18 days and 21 days, each paw volume of both    hind paws was measured with a plethysmometer.-   4) A test was carried out in the same manner as in 1) to 3) except    that the 1% aqueous methyl cellulose solution was used instead of    the test compound suspension, and its result was used as a control.    Method of Evaluation

Each paw edema inhibition rate of paw edema in an adjuvant-untreated paw(secondary inflammation paw) in each test compound administration groupwas calculated to paw edema in a secondary inflammation paw in a controlgroup, and antiarthritic effects of the present compounds were evaluatedusing the obtained rates as indexes.

Calculation of Paw Edema Inhibition Rates

Paw edema rates were calculated from the following calculation equation1, and then paw edema inhibition rates (the average of eight rats pergroup), which are indexes of the antiarthritic effects, were calculatedfrom the calculation equation 2.

Calculation Equation 1Paw edema rate (%)=(Paw volume after adjuvant treatment/paw volumebefore adjuvant treatment)×100Calculation Equation 2Paw edema inhibition rate (%)=100−{(Sx−100)/(So−100)}×100

-   So: Paw edema rate of control group-   Sx: Paw edema rate of test compound suspension administration group    Test Results and Discussion

As examples of test results, Table 3 shows paw edema inhibition rates(%) of test compounds (Compound Nos. 1-22, 1-38, 1-54, 1-104, 1-106,1-137, 1-158 and 4-4) obtained 21 days after.

TABLE 3 Paw edema Compound inhibition rate (%) 1-22 27 1-38 25 1-54 601-104 32 1-106 46 1-137 39 1-158 22 4-4 21

As shown in Table 3, the present compounds demonstrated paw edemainhibitory actions. Accordingly, the present compounds have excellentantiarthritic effects.

4. Evaluation Tests of Choroidal Neovascularization Inhibitory Effects

As one of widely-used methods of evaluating choroidal neovascularizationinhibitory effects of drugs, a neovascularization incidence test usingrat choroidal neovascularization models was reported in Graefe's Arch.Cli. Exp. Ophthalmol., 235, 313-319(1997). According to the methoddescribed in the above-mentioned literature, neovascularizationincidence tests of the present compounds were carried out, ratios ofneovascularization incidence rates of present compounds administrationgroups were calculated to a neovascularization incidence rate of vehicleadministration group (control group), and choroidal neovascularizationinhibitory effects of the present compounds were evaluated using theobtained ratios as indexes.

Preparation of Test Compound Solutions

A 1% aqueous methyl cellulose solution was added to each test compoundto suspend it thereby to prepare a 6 mg/10 ml test compound suspension.

Preparation of Laser-Induced Rat Choroidal Neovascularization Models

-   1) A 7:1 mixed solution (1 ml/kg) of a 5% ketamine hydrochloride    injection and a 2% xylazine hydrochloride injection was administered    intramuscularly to rats (Brown Norway, male, eight weeks old,    weight: 200 to 250 g) to anesthetize them systemically.-   2) A tropicamide-phenylephrine hydrochloride ophthalmic solution    (trade name: Mydrin-P) was instilled into eyes to cause mydriasis,    and then photocoagulation was performed in a Bruch's membrane of    each rat using a krypton laser photocoagulation apparatus. The laser    irradiation was carried out at eight spots per eye sparsely avoiding    thick retinal vessels in a posterior section of ocular fundus and    focusing on the retinal deep site. Photocoagulation conditions were    adjusted to 100 μm of spot size, 100 mM of output and 0.1 sec. of    coagulation time.-   3) After the photocoagulation, the ocular fundus was photographed to    confirm photocoagulation (laser irradiation) sites.    Method of Test and Method of Measurement-   1) From the laser irradiation day (i.e. zero day) to sixth day, the    test compound suspension (30 mg/kg/day) was administered orally once    a day for seven days every day.-   2) As the vehicle administration group (control group), a test was    carried out in the same manner as in 1) except that the 1% aqueous    methyl cellulose solution was used instead of the test compound    suspension, and its result was used as a control.    Method of Evaluation-   1) Seven days after the photocoagulation, 0.1 ml of a 10% aqueous    fluorescein solution was injected into a tail vein of the rat, and    fluorescein fundus photography was performed.-   2) Next, in the fluorescein fundus photography, a spot where    fluorescence leak was not observed was judged as negative, and a    spot where fluorescence leak was observed was judged as positive.    Photocoagulation sites where a little fluorescence leak was observed    were judged as positive when two sites are present.-   3) Neovascularization incidence rates were calculated according to    the calculation equation 1. Ratios of the neovascularization    incidence rates of the test compound administration groups to that    of the vehicle administration group were calculated according to the    calculation equation 2 from neovascularization incidence rates of    respective administration groups.    Neovascularization incidence rate (%)=(Positive photocoagulation    site number/total photocoagulation site number)×100  Calculation    Equation 1    Ratio of neovascularization incidence rate of test compound    administration group to that of vehicle administration group    (control group)(% of control)=Ax/Ao×100  Calculation Equation 2-   Ao: Neovascularization incidence rate of vehicle administration    group (control group) (% of control)-   Ax: Neovascularization incidence rate of test compound    administration group    Test Results and Discussion

As examples of test results, Table 4 shows ratios (% of control) of theneovascularization incidence rates of the test compound (Compound Nos.1-21, 1-23, 1-54, 1-80, 1-106, 1-136, 1-137, 1-296 and 4-4)administration groups to that of the vehicle administration group(control group)

TABLE 4 Ratio of neovascularization Compound incidence rate (% ofControl) 1-21 15 1-23 26 1-54 51 1-80 18 1-106 22 1-136 38 1-137 651-296 24 4-4 26The values are the average of three to four individuals and six to eighteyes.

As shown in Table 4, the present compounds demonstrate lowerneovascularization incidence rates than that of the vehicle and havechoroidal neovascularization inhibitory effects.

Industrial Applicability

The present invention provides therapeutic agents for diseases in whichangiogenesis or augmentation of vascular permeability is involved,particularly as therapeutic agents for cancer, rheumatoid arthritis,age-related macular degeneration, diabetic retinopathy, retinopathy ofprematurity, retinal vein occlusion, polypoid choroidal angiopathy,diabetic macular edema, psoriasis vulgaris, pultaceous arteriosclerosisand the like.

What is claimed is:
 1. A compound represented by the following formula[I] or a pharmaceutically acceptable salt thereof:

wherein the ring A is an aromatic five-membered heterocycle whichoptionally is fused with a cycloalkane ring, with the proviso that thering A is not a triazole ring; B is an alkylene; Rand R² are the same ordifferent, and are hydrogen, hydroxy, substituted or unsubstitutedalkoxy, substituted or unsubstituted aryloxy, unsubstituted alkyl,substituted or unsubstituted cycloalkyl, substituted or unsubstitutedaryl, substituted or unsubstituted heterocycle, amino, substituted orunsubstituted alkylamino, substituted or unsubstituted arylamino,substituted or unsubstituted acyl or an alkyl substituted by one or moregroups selected from the group consisting of halogen, hydroxy, alkoxy,aryloxy, cycloalkyl, alkenyl, unsubstituted aryl, aryl substituted byhalogen, aryl substituted by alkoxy, a heterocycle, amino, alkylamino,arylamino, mercapto, alkylthio, arylthio, formyl, alkylcarbonyl,arylcarbonyl, cyano and nitro; or R¹ and R² join together to form asubstituted or unsubstituted heterocycle; X and Y are the same ordifferent and are one or more groups selected from the group consistingof hydrogen, halogen, hydroxy, substituted or unsubstituted alkoxy,substituted or unsubstituted aryloxy, substituted or unsubstitutedalkyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted aryl, mercapto, substituted or unsubstituted alkylthio,substituted or unsubstituted arylthio, carboxyl, an ester of carboxyl,an amide of carboxyl, cyano and nitro; p is 0, 1 or 2; and q is 0 or 1.2. The compound or a pharmaceutically acceptable salt thereof as claimedin claim 1, wherein the ring A is an aromatic five-membered heterocycleand is a pyrrole ring, a pyrazole ring, an imidazole ring, a furan ring,a thiophene ring, an oxazole ring, an isoxazole ring, a thiazole ring oran isothiazole ring.
 3. The compound or a pharmaceutically acceptablesalt thereof as claimed in claim 1, wherein the ring A is an aromaticfive-membered heterocycle which is fused with a cycloalkane ring, andthe cycloalkane ring is a cyclopentane ring, a cyclohexane ring, acycloheptane ring or a cyclooctane ring.
 4. The compound or apharmaceutically acceptable salt thereof as claimed in claim 1, whereinthe ring A is a pyrrole ring, a pyrazole ring, an imidazole ring, afuran ring, a thiophene ring, an oxazole ring, an isoxazole ring, athiazole ring, an isothiazole ring, a tetrahydroindole ring, atetrahydrobenzofuran ring or a tetrahydrobenzo[b]thiophene ring.
 5. Thecompound or a pharmaceutically acceptable salt thereof as claimed inclaim 1, wherein the ring A is a pyrazole ring, a furan ring, athiophene ring or tetrahydrobenzo[b]thiophene ring.
 6. The compound or apharmaceutically acceptable salt thereof as claimed in claim 1, whereinring A is an aromatic five-membered heterocycle which optionally isfused with a cycloalkane ring, and a partial structure [C]

and a partial structure [D]

are bonded to adjacent carbon atoms on the ring A.
 7. The compound or apharmaceutically acceptable salt thereof as claimed in claim 6, whereinpositions of the carbon atoms are an α-position and β-where position tothe heteroatom on the ring A.
 8. The compound or a pharmaceuticallyacceptable salt thereof as claimed in claim 1, wherein R¹ and R² are thesame or different and are hydrogen, substituted or unsubstituted alkoxy,unsubstituted alkyl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted aryl, substituted or unsubstitutedheterocycle, substituted or unsubstituted alkylamino, substituted orunsubstituted arylamino or an alkyl substituted by one or more groupsselected from the group consisting of halogen, hydroxy, alkoxy, aryloxy,cycloalkyl, alkenyl, unsubstituted aryl, aryl substituted by halogen,aryl substituted by alkoxy, a heterocycle, amino, alkylamino, arylamino,mercapto, alkylthio, arylthio, formyl, alkylcarbonyl, arylcarbonyl,cyano and nitro; or R¹ and R² join together to form a substituted orunsubstituted heterocycle; X and Y are one or more groups selected fromthe group consisting of hydrogen, halogen, substituted or unsubstitutedalkoxy, substituted or unsubstituted alkyl, substituted or unsubstitutedalkylthio, carboxyl, an ester of carboxyl, an amide of carboxyl andcyano; and p is 0 or
 1. 9. The compound or a pharmaceutically acceptablesalt thereof as claimed in claim 1, wherein R¹ is hydrogen, substitutedalkoxy, unsubstituted alkyl, unsubstituted cycloalkyl, substituted orunsubstituted aryl, substituted or unsubstituted heterocycle,unsubstituted alkylamino, substituted arylamino or an alkyl substitutedby one or more groups selected from the group consisting of halogen,hydroxy, alkoxy, aryloxy, cycloalkyl, alkenyl, unsubstituted aryl, arylsubstituted by halogen, aryl substituted by alkoxy, a heterocycle,amino, alkylamino, arylamino, mercapto, alkylthio, arylthio, formyl,alkylcarbonyl, arylcarbonyl, cyano and nitro; R² is hydrogen,unsubstituted alkyl or an alkyl substituted by one or more groupsselected from the group consisting of halogen, hydroxy, alkoxy, aryloxy,cycloalkyl, alkenyl, unsubstituted aryl, aryl substituted by halogen,aryl substituted by alkoxy, a heterocycle, amino, alkylamino, arylamino,mercapto, alkylthio, arylthio, formyl, alkylcarbonyl, arylcarbonyl,cyano and nitro; or R¹ and R² join together to form a substituted orunsubstituted heterocycle; X is one or more groups selected from thegroup consisting of hydrogen, halogen and unsubstituted alkyl; Y is oneor more groups selected from the group consisting of hydrogen, halogen,substituted or unsubstituted alkoxy, unsubstituted alkyl, unsubstitutedalkylthio, carboxyl, an ester of carboxyl, an amide of carboxyl andcyano; and p is 0 or
 1. 10. A compound or a pharmaceutically acceptablesalt thereof, the compound being selected from the group consisting ofN-(4-isopropoxyphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide,N-(3-fluoro-4-methylphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide,N-(3-chlorophenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide,N-(4-chlorophenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide, 3-(2-chloropyridin-4-ylmethylthio)-N-(3,5-dimethphenyl)thiophene-2-carboxamide,N-(4-fluoro-3-methylphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide,N-(3,4-dimethylphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide,3-(4-pyridylmethylthio)-N-(4-trifluoromethylphenyl)-thiophene-2-carboxamide,N-(4-tert-butylphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide,N-(3-methylphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide,N-(3,4-difluorophenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide,N-(4-n-propylphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide,3-(4-pyridylmethylthio)-N-(4-trifluoromethoxyphenyl)-thiophene-2-carboxamide,N-(3-isoquinolyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide,N-(3,5-dimethylphenyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide,3-(4-pyridylmethylthio)-N-(3-trifluoromethylphenyl)-thiophene-2-carboxamide,N-(5-indanyl)-3-(4-pyridylmethylthio)thiophene-2-carboxamide,N-(4-chlorophenyl)-2-(4-pyridylmethylthio)thiophene-3-carboxamide,N-(3-methylphenyl)-2-(4-pyridylmethylthio)thiophene-3-carboxamide,N-(5-indanyl)-2-(4-pyridylmethylthio)thiophene-3-carboxamide,N-(4-bromo-3-methylphenyl)-2-(4-pyridylmethylthio)-thiophene-3-carboxamide,2-(4-pyridylmethylthio)-N-(4-trifluoromethylphenyl)-thiophene-3-carboxamide,N-(3,5-dimethylphenyl)-2-(4-pyridylmethylthio)thiophene-3-carboxamide,and N-(3-methylphenyl)-4-(4-pyridylmethylthio)thiophene-3-carboxamide.11. A pharmaceutical composition comprising a pharmaceutically effectiveamount of the compound or a pharmaceutically acceptable salt thereof asclaimed in claim 1 in combination with a pharmaceutically acceptablecarrier.
 12. A pharmaceutical composition comprising a pharmaceuticallyeffective amount of the compound or a pharmaceutically acceptable saltthereof as claimed in claim 10, in combination with a pharmaceuticallyacceptable carrier.
 13. A method of treating a disease in whichangiogenesis or augmentation of vascular permeability is involvedcomprising administering to a patient an effective amount for treatmentof the compound or a pharmaceutically acceptable salt thereof as claimedin claim 1 wherein the disease is selected from the group consisting ofrheumatoid arthritis, age-related macular degeneration, diabeticretinopathy, retinopathy of prematurity, retinal vein occlusion,polypoid choroidal angiopathy, diabetic macular edema, psoriasisvulgaris and pultaceous arteriosclerosis.
 14. A method of treating adisease in which angiogenesis or augmentation of vascular permeabilityis involved comprising administering to a patient an effective amountfor treatment of the compound or a pharmaceutically acceptable saltthereof as claimed in claim 10 wherein the disease is selected from thegroup consisting of rheumatoid arthritis, age-related maculardegeneration, diabetic retinopathy, retinopathy of prematurity, retinalvein occlusion, polypoid choroidal angiopathy, diabetic macular edema,psoriasis vulgaris and pultaceous arteriosclerosis.